Search

BACKGROUND: We recently reported that the dopamine (DA) analogue CA140 modulates neuroinflammatory responses in lipopolysaccharide-injected wild-type (WT) mice and in 3-month-old 5xFAD mice, a model of Alzheimers disease (AD). However, the effects of CA140 on Aβ/tau pathology and synaptic/cognitive function and its molecular mechanisms of action are unknown. METHODS: To investigate the effects of CA140 on cognitive and synaptic function and AD pathology, 3-month-old WT mice or 8-month-old (aged) 5xFAD mice were injected with vehicle (10% DMSO) or CA140 (30 mg/kg, i.p.) daily for 10, 14, or 17 days. Behavioral tests, ELISA, electrophysiology, RNA sequencing, real-time PCR, Golgi staining, immunofluorescence staining, and western blotting were conducted. RESULTS: In aged 5xFAD mice, a model of AD pathology, CA140 treatment significantly reduced Aβ/tau fibrillation, Aβ plaque number, tau hyperphosphorylation, and neuroinflammation by inhibiting NLRP3 activation. In addition, CA140 treatment downregulated the expression of cxcl10, a marker of AD-associated reactive astrocytes (RAs), and c1qa, a marker of the interaction of RAs with disease-associated microglia (DAMs) in 5xFAD mice. CA140 treatment also suppressed the mRNA levels of s100β and cxcl10, markers of AD-associated RAs, in primary astrocytes from 5xFAD mice. In primary microglial cells from 5xFAD mice, CA140 treatment increased the mRNA levels of markers of homeostatic microglia (cx3cr1 and p2ry12) and decreased the mRNA levels of a marker of proliferative region-associated microglia (gpnmb) and a marker of lipid-droplet-accumulating microglia (cln3). Importantly, CA140 treatment rescued scopolamine (SCO)-mediated deficits in long-term memory, dendritic spine number, and LTP impairment. In aged 5xFAD mice, these effects of CA140 treatment on cognitive/synaptic function and AD pathology were regulated by dopamine D1 receptor (DRD1)/Elk1 signaling. In primary hippocampal neurons and WT mice, CA140 treatment promoted long-term memory and dendritic spine formation via effects on DRD1/CaMKIIα and/or ERK signaling. CONCLUSIONS: Our results indicate that CA140 improves neuronal/synaptic/cognitive function and ameliorates Aβ/tau pathology and neuroinflammation by modulating DRD1 signaling in primary hippocampal neurons, primary astrocytes/microglia, WT mice, and aged 5xFAD mice.

Drugs of abuse can persistently change the reward circuit in ways that contribute to relapse behavior, partly via mechanisms that regulate chromatin structure and function. Nuclear orphan receptor subfamily4 groupA member2 (NR4A2, also known as NURR1) is an important effector of histone deacetylase 3 (HDAC3)-dependent mechanisms in persistent memory processes and is highly expressed in the medial habenula (MHb), a region that regulates nicotine-associated behaviors. Here, expressing the Nr4a2 dominant negative (Nurr2c) in the MHb blocks reinstatement of cocaine seeking in mice. We use single-nucleus transcriptomics to characterize the molecular cascade following Nr4a2 manipulation, revealing changes in transcriptional networks related to addiction, neuroplasticity, and GABAergic and glutamatergic signaling. The network controlled by NR4A2 is characterized using a transcription factor regulatory network inference algorithm. These results identify the MHb as a pivotal regulator of relapse behavior and demonstrate the importance of NR4A2 as a key mechanism driving the MHb component of relapse.

• Type 1 diabetes reduces exploration without reducing novelty-seeking motivation. • Deletion of TNFR1 attenuates the reduction in gait speed induced by type 1 diabetes. • Type 1 diabetes induces anxiety-like behavior in the first week post-streptozotocin. • Deletion of TNFR1 induces working memory impairment in normoglycemic mice. Type 1 diabetes mellitus (T1D) is associated with cognitive impairments in humans. A well-established animal model of T1D is induced through the administration of streptozotocin (STZ), a glucose analog that induces pancreatic β-cell death, resulting in hyperglycemia and cognitive impairment linked to neuroinflammation and oxidative stress. Tumor necrosis factor (TNF)-α, a key inflammatory mediator, is elevated in the central nervous system (CNS) of diabetic animals. In this study, we utilized TNFR1 knockout mice to investigate the role of TNFR1 signaling in short-term T1D-related cognitive impairment. Our findings showed that diabetic animals did not develop cognitive damage within the first 2 weeks of T1D but exhibited reduced exploration in all behavioral tests. Our findings suggest that this reduction in exploration was attributable to motor impairment, as there was no reduction in motivated novelty-seeking behavior. Additionally, deletion of TNFR1 signaling attenuated gait speed impairment in diabetic mice, but did not affect other motor-related or exploratory behaviors. [ABSTRACT FROM AUTHOR]

Magnetic fields are widely used in medical diagnostics because of their superior non-invasive properties. In addition, with the widespread use of magnetic fields in transportation and other areas, their potential hazards to human health and the assessment of their safety have attracted considerable attention. The effects of magnetic fields on living organisms have a long history. The biological effects of magnetic field exposure in mice and rats depend on the magnetic field strength, exposure time, and direction; depending on these and potentially other factors, magnetic fields can cause a series of neurobiological effects. We reviewed global research on the neurobiological effects of magnetic fields from recent years to provide an overview and insights into the underlying mechanisms. This review focuses on the biological effects of static and dynamic magnetic fields of different frequencies and intensities on animals and nerve cells and their mechanisms of action. [ABSTRACT FROM AUTHOR]

Background: Ferroptosis represents a nonapoptotic type of programmed cell death induced by excessive intracellular iron accumulation. Ferroptosis is an essential driver of the pathogenesis of Alzheimer's disease (AD). Tetrahedral framework nucleic acids (tFNAs) are a novel type of nanoparticle with superior antiapoptotic capacity and excellent biocompatibility. However, the effect of tFNAs on Aβ triggered ferroptosis, cognitive and synaptic impairments in AD remains unknown. Methods: N2a cells were treated with Aβ combined with/without tFNAs. Cell viability and levels of Fe2+, lipid peroxidation, MDA, LDH, and GSH were examined. RNA sequencing was applied to explore dysregulated ferroptosis related genes. Seven-month-old APP/PS1 mice were intranasally administrated with tFNAs for two weeks. Fluorescence imaging was used to detect the tFNAs distribution in the brain. Novel object recognition (NOR) test followed by Morris water maze (MWM) was used to test the learning and memory performance of mice. Golgi staining, Western blot, and immunofluorescence staining were used to examine synaptic plasticity. Results: tFNAs promoted cell viability and GSH levels, reduced the levels of Fe2+, lipid peroxidation, MDA, and LDH in N2a cells treated with Aβ. RNA sequencing revealed that tFNAs reversed the promotive effect of Aβ on ferroptosis driver Atf3 gene and suppressive effect on ferroptosis suppressors Rrm2 and Furin genes. Fluorescence imaging confirmed the brain infiltration of tFNAs. tFNAs rescued synaptic and memory impairments, and ferroptosis in seven-month-old APP/PS1 mice. Conclusions: Collectively, tFNAs inhibited Aβ-mediated ferroptosis and ameliorated cognitive and synaptic impairments in AD mice. tFNAs may serve as novel option to deal with AD. [ABSTRACT FROM AUTHOR]

Dynamic gain control of aversive signals enables adaptive behavioral responses. Although the role of amygdalar circuits in aversive processing is well established, the neural pathway for amplifying aversion remains elusive. Here, we show that the brainstem circuit linking the interpeduncular nucleus (IPN) with the nucleus incertus (NI) amplifies aversion and promotes avoidant behaviors. IPN GABA neurons are activated by aversive stimuli and their predicting cues, with their response intensity closely tracking aversive values. Activating these neurons does not trigger aversive behavior on its own but rather amplifies responses to aversive stimuli, whereas their ablation or inhibition suppresses such responses. Detailed circuit dissection revealed anatomically distinct subgroups within the IPN GABA neuron population, highlighting the NI-projecting subgroup as the modulator of aversiveness related to fear and opioid withdrawal. These findings unveil the IPN-NI circuit as an aversion amplifier and suggest potential targets for interventions against affective disorders and opioid relapse. • IPN GABA neurons encode aversive value • The activity of these neurons amplifies aversive responses • The IPN-NI pathway controls aversive evaluation and fear learning • This pathway strengthens the aversive response to opioid withdrawal Liang et al. demonstrate that the brainstem circuit from the interpeduncular nucleus (IPN) to the nucleus incertus (NI) is an aversion amplifier, offering potential therapeutic targets for affective disorders and opioid relapse prevention. [ABSTRACT FROM AUTHOR]

The article discusses the importance of integrating physiological approaches into evolutionary studies to understand functional evolution and biodiversity. It emphasizes the need for real-time physiological studies in natural habitats to explore the evolution of behaviors, learning, and memory at the cellular-molecular level. The authors argue that the physiology of evolution should be a fundamental part of biomedical education and interdisciplinary research to advance scientific understanding and address societal challenges. The article highlights the historical context of evolutionary physiology and calls for a renewed focus on integrative approaches to study evolutionary processes. [Extracted from the article]

Hippocampal-dependent memory is known to emerge late in ontogeny, and its full development is protracted. Yet the changes in hippocampal neuronal function that underlie this delayed and gradual maturation remain relatively unexplored. To address this gap, we recorded ensembles of CA1 neurons while charting the development of hippocampal-dependent spatial working memory (WM) in rat pups (∼2–4 weeks of age). We found a sharp transition in WM development, with age of inflection varying considerably between individual animals. In parallel with the sudden emergence of WM, hippocampal spatial representations became abruptly task specific, remapping between encoding and retrieval phases of the task. Further, we show how the development of task-phase remapping could partly be explained by changes in place-field size during this developmental period as well as the onset of precise temporal coordination of CA1 excitatory input. Together, these results suggest that a hallmark of hippocampal memory development may be the emergence of contextually specific CA1 representations driven by the maturation of CA1 micro-circuits. [Display omitted] • Hippocampal spatial working memory (SWM) develops overnight in rat pups • As SWM matures, place cell non-spatial coding emerges (task-phase remapping) • These changes occur in tandem with the emergence of precise CA1 spatial tuning • These developmental milestones may reflect the maturation of CA1 input coordination Bevandić et al. show that hippocampal spatial working memory develops abruptly in rat pups and the age of inflection varies between animals. As SWM emerged, CA1-place cell coding of non-spatial variables matured and spatial tuning became adult-like. These developmental milestones occurred as temporal coordination of CA1 inputs became more precise. [ABSTRACT FROM AUTHOR]

Learning alterations in the child population may be linked to gestational diabetes as a causal factor, though this remains an open and highly controversial question. In that sense, it has been reported that maternal hyperglycemia generates a threatening condition that affects hippocampal development in offspring. The pyramidal cells of the CA3 subfield, a key structure in learning and memory processes, are particularly important in cognitive deficiencies. We evaluate the effect of the hyperglycemic intrauterine environment on hippocampal histomorphometry in offspring, correlating it with spatial learning and memory, as well as the morphology of dendrites and spines in 30-day-old pups (P30). The maternal hyperglycemia affected the body weight, height, and brain size of fetuses at 21 days of gestation (F21), newborn pups (P0) and P30 pups from diabetic rats, which were smaller compared to the control group. Consequently, this resulted in a decrease in hippocampal size, lower neuronal density and cytoarchitectural disorganization in the CA3 region of the hippocampus in the offspring at the three ages studied. The behavioral tests performed showed a direct relationship between morpho-histological alterations and deficiencies in learning and memory, as well as alterations in the morphology of the dendrites and spines. Therefore, knowing the harmful effects caused by gestational diabetes can be of great help to establish therapeutic and educational strategies that can help to improve learning and memory in children. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a common age-associated progressive neurodegenerative disorder that is implicated in the aberrant regulation of numerous circular RNAs (circRNAs). Here, we reported that circ-Bptf, a conserved circRNA derived from the Bptf gene, showed an age-dependent decrease in the hippocampus of APP/PS1 mice. Overexpression of circ-Bptf significantly reversed dendritic spine loss and learning and memory impairment in APP/PS1 mice. Moreover, we found that circ-Bptf was predominantly localized to the cytoplasm and upregulated p62 expression by binding to miR-138-5p. Furthermore, the miR-138-5p mimics reversed the decreased expression of p62 induced by the silencing of circ-Bptf. Together, our findings suggested that circ-Bptf ameliorated learning and memory impairments via the miR-138-5p/p62 axis in APP/PS1 mice. It may act as a potential player in AD pathogenesis and therapy. [ABSTRACT FROM AUTHOR]

Neuronal connectivity is essential for adaptive brain responses and can be modulated by dendritic spine plasticity and the intrinsic excitability of individual neurons. Dysregulation of these processes can lead to aberrant neuronal activity, which has been associated with numerous neurological disorders including autism, epilepsy, and Alzheimer's disease. Nonetheless, the molecular mechanisms underlying abnormal neuronal connectivity remain unclear. We previously found that the serine/threonine kinase Microtubule Affinity Regulating Kinase 2 (MARK2), also known as Partitioning Defective 1b (Par1b), is important for the formation of dendritic spines in vitro. However, despite its genetic association with several neurological disorders, the in vivo impact of MARK2 on neuronal connectivity and cognitive functions remains unclear. Here, we demonstrate that the loss of MARK2 in vivo results in changes to dendritic spine morphology, which in turn leads to a decrease in excitatory synaptic transmission. Additionally, the loss of MARK2 produces substantial impairments in learning and memory, reduced anxiety, and defective social behavior. Notably, MARK2 deficiency results in heightened seizure susceptibility. Consistent with this observation, electrophysiological analysis of hippocampal slices indicates underlying neuronal hyperexcitability in MARK2‐deficient neurons. Finally, RNAseq analysis reveals transcriptional changes in genes regulating synaptic transmission and ion homeostasis. These results underscore the in vivo role of MARK2 in governing synaptic connectivity, neuronal excitability, and cognitive functions. [ABSTRACT FROM AUTHOR]

ABSTRACT Neonicotinoids (NNIs) are the most commonly used insecticides in the world and clothianidin, a type of NNI, is commonly found in honey bee collected pollen. Clothianidin has several negative effects on honey bee health and behaviour, but whether and how it might impact learning and memory remains unclear. Therefore, we exposed honey bee workers to a field‐realistic oral dose of clothianidin for 7 days to assess their sugar responsiveness, and olfactory learning and memory using the proboscis extension response paradigm. Sugar responsiveness impacts important colony‐level traits, such as onset of foraging, that help maintain colony homeostasis as well as impacts learning and memory. We then measured how clothianidin alters protein expression in the brain in an effort to understand the mechanism(s) of clothianidin's effects. Clothianidin‐exposed bees had impaired sugar responsiveness, but no effect was seen on learning and memory. We identified 5069 protein groups and showed that the exposed bees had fewer detectable proteins. The exposed bees also had fewer mitochondrial respiration proteins, as well as reduced levels of nicotinic acetylcholine receptor α7 (nAChRα7) subunit (one of the targets of clothianidin) and reduced levels of acetylcholinesterase and acetylcholinesterase‐2 levels. In the exposed bees, the levels of nAChRα7 subunit positively correlated with sugar responsiveness, providing evidence for a possible mechanical explanation. [ABSTRACT FROM AUTHOR]

It is estimated that 1 in 36 children are affected by autism spectrum disorder (ASD) in the United States, which is nearly a twofold increase from a decade ago. Recent genetic studies have identified de novo loss‐of‐function (dnLoF) mutations in the Down Syndrome Cell Adhesion Molecule (DSCAM) as a strong risk factor for ASD. Previous research has shown that DSCAM ablation confers social interaction deficits and perseverative behaviors in mouse models. However, it remains unknown to what extent DSCAM underexpression captures the full range of behaviors, specifically cognitive phenotypes, presented in ASD. Here, we conducted a comprehensive cognitive behavioral phenotyping which revealed that loss of one copy of DSCAM, as in the DSCAM2J+/−, that is, DSCAM heterozygous mice, displayed hyperactivity, increased anxiety‐like behavior, and motor coordination deficits. Additionally, hippocampal‐dependent learning and memory was affected, including impairments in working memory, long‐term memory, and contextual fear learning. Interestingly, implicit learning processes remained intact. Therefore, DSCAM LoF produces autistic‐like behaviors that are similar to those observed in human cases of ASD. These findings further support a role for DSCAM dnLoF mutations in ASD and suggest DSCAM2J+/− as a suitable model for ASD research. [ABSTRACT FROM AUTHOR]

Simple Summary: Surgical castration is a common practice for controlling animal reproduction. However, surgical castration can cause pain and stress and may even lead to psychological harm. As an alternative, GnRH vaccines can lower androgen levels without surgery. In this study, we compared the effects of a newly developed GnRH vaccine and surgical castration in rats. Both methods effectively suppressed sexual behavior, but surgical castration resulted in significant depression and social withdrawal, while the vaccinated rats did not exhibit these behavioral issues. This suggests that GnRH immunocastration may be a more humane method that better aligns with animal welfare standards. Castration is often employed in animal management for reproductive control. However, it is important to evaluate its impact on animal welfare. In this study, we developed rat models for both surgical (n = 6) and GnRH immunocastration (n = 6) to assess the effects of these castration methods on physiological and behavioral characteristics. The novel GnRH-based vaccine significantly increased serum GnRH antibody levels and drastically reduced testosterone, with the testes shrinking to one-fifth the size of those in the control group, thereby halting spermatogenesis at the secondary spermatocyte stage. Behavioral evaluations demonstrated that sexual behavior was significantly suppressed in both surgically and immunologically castrated groups compared to the control, confirming the effectiveness of both methods. However, psychological tests revealed significant signs of depression and social deficits in the surgically castrated group, whereas the behavior of the GnRH-immunocastrated group did not significantly differ from the control. Furthermore, no significant differences in learning and memory were observed among the three groups in the water maze test. Compared to surgical castration, GnRH immunocastration offers effective results and better animal welfare, providing a more humane alternative for livestock management. [ABSTRACT FROM AUTHOR]

Rationale: Alzheimer's disease (AD), an age-dependent devastating neuropsychiatric disorder, is a leading cause of learning, memory and intellectual disabilities. Current therapeutic approaches for the amelioration of the anomalies of AD are not effective. Objective: In the present study, the molecular mechanisms underlying sporadic AD (sAD), the memory related behavioral analysis and neuroprotective effects of Ellagic acid (EA) were investigated. Method: sAD mouse model was developed by intracerebroventricular (ICV) injection of Streptozotocin (STZ). The efficacy of EA, a naturally occurring polyphenol, in amelioration of anomalies associated with sAD was assessed. EA was administered once daily for 28 days at a dose of 75 mg/kg body weight followed by neurobehavioral, biochemical, molecular and neuronal count analysis to delineate the mode of action of EA. Result: The ICV injection of STZ in mice significantly increased the expression of AD biomarkers in addition to enhanced oxidative stress. A decline in the discrimination index in Novel Object Recognition Test was observed indicating the compromise of recognition memory in AD. Studies on the expression of genes involved in synaptic plasticity reveal the dysregulation of the α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of the glutamate and its scaffolding proteins in the postsynaptic density and thereby synaptic plasticity in AD. ICV-STZ led to significant upregulation of apoptotic markers which led to decrease in neuronal density of the cerebral cortex. EA significantly reversed the above and improved anomalies of sAD. Conclusion: EA was observed to profoundly modulate the genes involved in AD pathophysiology, restored antioxidant enzymes activity, reduced lipid peroxidation and neuronal loss in the sAD brain. Further, EA was observed to effectively modulate the genes involved in apoptosis and synaptic plasticity. Therefore, EA possesses promising anti-AD properties, which may improve AD-associated anomalies by modulating synaptic plasticity via AMPAR signaling. [ABSTRACT FROM AUTHOR]

The aggregation of Amyloid- β (A β) peptides is associated with neurodegeneration in Alzheimer's disease (AD). We previously identified novel naphtalene derivatives, including the lead compound Amylovis-201, able to form thermodynamically stable complexes with A β species, peptides and fibrils. As the drug showed a chemical scaffold coherent for an effective interaction with the σ 1 receptor chaperone and as σ 1 agonists are currently developed as potent neuroprotectants in AD, we investigated the pharmacological action of Amylovis-201 on the σ 1 receptor. We report that Amylovis-201 is a potent σ 1 agonist by several in silico , in vitro and in vivo assays and that its anti-amnesic and neuroprotective effects involve a pharmacological action at σ 1 receptors. Furthermore, we show for the first time that classical σ 1 receptor agonist (PRE-084), and antagonist (NE-100) are able to interact and disaggregate A β 25–35 fibrils. Interestingly, Amylovis-201 was the only compound inhibiting A β 25–35 aggregates formation. Our results therefore highlight a dual action of Amylovis-201 as anti-aggregating agent and σ 1 receptor agonist that could be highly effective in long-term treatment against neurodegeneration in AD. Amylovis-201, known to interfere with Amyloid- β aggregation, also acts as a sigma-1 agonist in vitro and in vivo. The drug is therefore a dual-acting compound with synergic extracellular and intracellular modes of action. [Display omitted] [ABSTRACT FROM AUTHOR]

Neurogenesis persists throughout adulthood in the hippocampus and contributes to specific cognitive functions. In Alzheimer's disease (AD), the hippocampus is affected by pathology and functional impairment early in the disease. Human AD patients have reduced adult hippocampal neurogenesis (AHN) levels compared to age‐matched healthy controls. Similarly, rodent AD models show a decrease in AHN before the onset of the classical hallmarks of AD pathology. Conversely, enhancement of AHN can protect against AD pathology and ameliorate memory deficits in both rodents and humans. Therefore, impaired AHN may be a contributing factor of AD‐associated cognitive decline, rather than an effect of it. In this review we outline the regulation and function of AHN in healthy individuals, and highlight the relationship between AHN dysfunction and cognitive impairments in AD. The existence of AHN in humans and its relevance in AD patients will also be discussed, with an outlook toward future research directions. Highlights: Adult hippocampal neurogenesis occurs in the brains of mammals including humans.Adult hippocampal neurogenesis is reduced in Alzheimer's disease in humans and animal models. [ABSTRACT FROM AUTHOR]

Summary This study aimed to examine the improvement in performance and functional magnetic resonance imaging correlates of motor learning after a daytime nap versus a period of resting wakefulness among individuals with traumatic brain injury. A sample of 32 individuals with traumatic brain injury was randomly assigned to a Sleep (N = 17) or Wake (N = 15) group after a period of training on a motor sequential learning task. A 45‐min nap opportunity was provided for the Sleep group, while the Wake group watched a documentary for 45 min. Performance at the end of training was compared with their performance after the nap or wake intervention. Before and after the intervention, the motor sequential learning task was completed in the magnetic resonance imaging scanner to examine the relationship between change in performance and neural activation. Participants in the Sleep group showed significant gains from the end of training to after the intervention, whereas the Wake group did not. The functional magnetic resonance imaging results showed that relative to the Wake group, the Sleep group showed significantly decreased activation post‐intervention in the anterior cingulate/paracingulate, cerebellum, cuneus/precuneus, and inferior parietal lobule including angular and supramarginal gyri. Importantly, across both groups, increased task performance at post‐intervention was associated with decreased activation in the anterior cingulate/paracingulate and cerebellum. This study demonstrated the enhancing effect of a nap on motor learning performance in a sample of individuals with traumatic brain injury, with patterns of neural activation suggesting that the sequence was more automatized in the Sleep group. Strategic placement of a nap after an intense period of motor learning in the medical rehabilitation setting may have important implications for maximizing recovery after traumatic brain injury. [ABSTRACT FROM AUTHOR]

The temperature-sensitive Drosophila mutant agnts3 exhibits the restoration of learning defects both after heat shock (HS) and under hypomagnetic conditions (HMC). Previously, agnts3 was shown to have an increased level of LIM kinase 1 (LIMK1). However, its limk1 sequence did not significantly differ from that of the wild-type strain Canton-S (CS). Here, we performed whole-genome and poly(A)-enriched transcriptome sequencing of CS and agnts3 males normally, after HMC, and after HS. Several high-effect agnts3-specific mutations were identified, including MED23 (regulation of HS-dependent transcription) and Spn42De, the human orthologs of which are associated with intellectual disorders. Pronounced interstrain differences between the transcription profiles were revealed. Mainly, they included the genes of defense and stress response, long non-coding RNAs, and transposons. After HS, the differences between the transcriptomes became less pronounced. In agnts3, prosalpha1 was the only gene whose expression changed after both HS and HMC. The normal downregulation of prosalpha1 and Spn42De in agnts3 was confirmed by RT-PCR. Analysis of limk1 expression did not reveal any interstrain differences or changes after stress. Thus, behavioral differences between CS and agnts3 both under normal and stressed conditions are not due to differences in limk1 transcription. Instead, MED23, Spn42De, and prosalpha1 are more likely to contribute to the agnts3 phenotype. [ABSTRACT FROM AUTHOR]

The developed human brain shows remarkable plasticity following perceptual learning, resulting in improved visual sensitivity. However, such improvements commonly require extensive stimuli exposure. Here we show that efficiently enhancing visual perception with minimal stimuli exposure recruits distinct neural mechanisms relative to standard repetition-based learning. Participants (n = 20, 12 women, 8 men) encoded a visual discrimination task, followed by brief memory reactivations of only five trials each performed on separate days, demonstrating improvements comparable with standard repetition-based learning (n = 20, 12 women, 8 men). Reactivation-induced learning engaged increased bilateral intraparietal sulcus (IPS) activity relative to repetition-based learning. Complementary evidence for differential learning processes was further provided by temporal–parietal resting functional connectivity changes, which correlated with behavioral improvements. The results suggest that efficiently enhancing visual perception with minimal stimuli exposure recruits distinct neural processes, engaging higher-order control and attentional resources while leading to similar perceptual gains. These unique brain mechanisms underlying improved perceptual learning efficiency may have important implications for daily life and in clinical conditions requiring relearning following brain damage. [ABSTRACT FROM AUTHOR]

Aim: To investigate the molecular mechanisms underlying memory impairment induced by high‐altitude (HA) hypoxia, specifically focusing on the role of cold‐inducible RNA‐binding protein (CIRP) in regulating the AMPA receptor subunit GluR1 and its potential as a therapeutic target. Methods: A mouse model was exposed to 14 days of hypobaric hypoxia (HH), simulating conditions at an altitude of 6000 m. Behavioral tests were conducted to evaluate memory function. The expression, distribution, and interaction of CIRP with GluR1 in neuronal cells were analyzed. The binding of CIRP to GluR1 mRNA and its impact on GluR1 protein expression were examined. Additionally, the role of CIRP in GluR1 regulation was assessed using Cirp knockout mice. The efficacy of the Tat‐C16 peptide, which consists of the Tat sequence combined with the CIRP 110‐125 amino acid sequence, was also tested for its ability to mitigate HH‐induced memory decline. Results: CIRP was primarily localized in neurons, with its expression significantly reduced following HH exposure. This reduction was associated with decreased GluR1 protein expression on the cell membrane and increased localization in the cytoplasm. The interaction between CIRP and GluR1 was diminished under HH conditions, leading to reduced GluR1 stability on the cell membrane and increased cytoplasmic relocation. These changes resulted in a decreased number of synapses and dendritic spines, impairing learning and memory functions. Administration of the Tat‐C16 peptide effectively ameliorated these impairments by modulating GluR1 expression and distribution in HH‐exposed mice. Conclusion: CIRP plays a critical role in maintaining synaptic integrity under hypoxic conditions by regulating GluR1 expression and distribution. The Tat‐C16 peptide shows promise as a therapeutic strategy for alleviating cognitive decline associated with HA hypoxia. [ABSTRACT FROM AUTHOR]

Postmenopausal women have a higher probability of experiencing cognitive alterations compared to men, suggesting that the decline in female hormones may contribute to cognitive deterioration. Thailand traditionally uses Tri-Kaysorn-Mas (TKM), a blend of three medicinal herbs, as a tonic to stimulate appetite and relieve dyspepsia. Due to its antioxidant and anti-acetylcholinesterase activities, we investigated the effects of TKM (50 and 100 mg/kg/day, p.o., for 8 weeks) on cognitive deficits and their underlying causes in an ovariectomized (OVX) mouse model of menopause. OVX mice showed cognitive impairment in the Y-maze, novel object recognition task (NORT), and Morris water maze (MWM) behavioral tests, along with atrophic changes to the uterus, altered levels of serum 17β-estradiol, and down-regulated expression of estrogen receptors (ERα and ERβ). These behavioral effects were reversed by TKM. TKM decreased malondialdehyde (MDA) levels and mitigated oxidative stress in the brain by enhancing the activity of superoxide dismutase (SOD) and catalase (CAT) and by up-regulating the antioxidant-related gene Nrf2 while down-regulating Keap1. TKM also counteracted OVX-induced neurodegeneration by enhancing the expression of the neurogenesis-related genes BDNF and CREB. The results indicate that TKM extract alleviates oxidative brain damage and neurodegeneration while enhancing cognitive behavior in OVX mice, significantly improving cognitive deficiencies related to menopause/ovariectomy through multiple targets. [ABSTRACT FROM AUTHOR]

Objective：To explore the possible mechanism of regular aerobic exercise in improving the learning and memory function in rats with middle cerebral artery occlusion reperfusion (MCAO/R). Method：Total of 36 SD rats were randomly divided into 3 groups：sham operation group (IS group), aerobic exercise group (AE group), and model group (IC group). MCAO/R models were established in the IC and AE groups, while the IS group underwent the same arterial dissection without occlusion. After model establishment, the rats in the AE group were trained on a treadmill for 14 days, while the rats in the IS group and IC group were only placed on the treadmill for the same duration without running. The neurological function of the rats in each group was scored, the cerebral infarction focus of the rats was observed by magnetic resonance imaging T2WI scanning before and after the intervention, and the recognition and memory ability of the rats was detected by the new object recognition experiment before and after the intervention. The Western Blot was used to detect the expression of NLRP3, caspase-1, and GSDMD in the hippocampus, and immunohistochemistry was used to detect the activation of microglia in the CA1 region of the ischemic hippocampus. The levels of IL-1β and IL-18 were detected by ELISA. The expression and co-localization of IBA1 with NLRP3, caspase-1, and GSDMD were detected by immunofluorescence co-labeling assay. Result：Before intervention, the neurological function score and the signal intensity of the left cerebral cortex hippocampus of the IC Group were significantly higher than that of the IS group (P<0.05), and the resolution of new objects decreased significantly (P<0.05). There were no significant differences between the AE and IC groups in the proportion of neurological deficit, cerebral infarction volume and novel object recognition rate (P>0.05). After 14 days of treadmill training intervention, compared with IC group, the AE group showed significantly lower neurological function scores (P<0.05), reduced the percentage of cerebral infarction volume (P<0.05), improved object recognition ability (P<0.05), improved pathology in hippocampal CA1 area, reduced microglia activation level (P<0.05), decreased levels of IL-1β and IL-18 (P<0.05), and significantly reduced expression of NLRP3, caspase-1 and GSDMD proteins (P<0.05). In addition, compared with the IC group, the accumulative optical density of NLRP3, GSDMD in CA1 and caspase-1 in CA3 regions of the ischemic hippocampus in the AE group was significantly decreased, and the number of IBA1 and NLRP3, IBA1 and GSDMD double-positive cells was significantly decreased (P<0.05). Conclusion： Regular aerobic exercise can improve the ability of recognition and memory in MCAO/R rats, which may be related to the inhibition of hippocampal microglia pyroptosis and activation. [ABSTRACT FROM AUTHOR]

Sleep is considered closely related to cognitive function, and cognitive impairment is the main clinical manifestation of Alzheimer's disease (AD). Sleep disturbance in AD patients is more severe than that in healthy elderly individuals. Additionally, sleep deprivation reportedly increases the activity of the hypothalamic orexin system and the risk of AD. To investigate whether intervention with the orexin system can improve sleep disturbance in AD and its impact on AD pathology. In this study, six-month-old amyloid precursor protein/presenilin 1 mice were subjected to six weeks of chronic sleep deprivation and injected intraperitoneally with almorexant, a dual orexin receptor antagonist (DORA), to investigate the effects and mechanisms of sleep deprivation and almorexant intervention on learning and memory in mice with AD. We found that sleep deprivation aggravated learning and memory impairment and increased brain β-amyloid (Aβ) deposition in mice with AD. The application of almorexant can increase the total sleep time of sleep-deprived mice and reduce cognitive impairment and Aβ deposition, which is related to the improvement in Aquaporin-4 polarity. Thus, DORA may be an effective strategy for delaying the progression of AD patients by improving the sleep disturbances. • Almorexant intervention can alleviate chronic sleep deprivation-induced AD learning and memory impairment and Aβ deposition. • The mechanism may be related to mitigating the damage to AQP4 polarity caused by sleep deprivation. • Orexin dual receptor antagonists can be an effective strategy for improving sleep in AD, and slowing pathological progression. [ABSTRACT FROM AUTHOR]

Although most cognitive impairments induced by prolonged alcohol consumption tend to improve within the initial months of abstinence, there is evidence suggesting certain cognitive deficits may persist. This study aimed to investigate the impact of aerobic exercise on learning and memory in alcohol use disorder (AUD) mice following a period of abstinence from alcohol. We also sought to assess the levels of monoamine neurotransmitters in the hippocampus. To this end, we established an AUD mouse model through a two‐bottle choice (sucrose fading mode and normal mode) and chronic intermittent alcohol vapor (combined with intraperitoneal injection) and randomly allocated mice into exercise groups to undergo treadmill training. Learning and memory abilities were assessed through the Morris water maze test and spontaneous activity was evaluated using the open field test. The levels of dopamine, norepinephrine, serotonin, and brain‐derived neurotrophic factor in the hippocampus were quantified using enzyme‐linked immunoassay (ELISA) kits. The findings reveal that after cessation of alcohol consumption, learning and memory abilities in AUD mice did not completely return to normal levels. The observed enhancement of cognitive functions in AUD mice through aerobic exercise may be attributed to restoring levels of monoamine neurotransmitters in the hippocampus, boosting brain‐derived neurotrophic factor (BDNF) concentrations, and facilitating an increase in hippocampal mass. These results offer empirical evidence to support aerobic exercise as a viable therapeutic strategy to alleviate cognitive deficits associated with AUD. [ABSTRACT FROM AUTHOR]

The JAK/STAT signalling pathway is essential for cell communication and gene expression, particularly in brain development. Its dysregulation relates to neurological conditions such as Down syndrome and Noonan syndrome, impacting the shift from neuron to astrocyte production. Ruxolitinib, an FDA-approved JAK1 and JAK2 inhibitor, is used to treat disorders associated with dysregulated JAK-STAT signaling. This study aimed to evaluate the possible effects of prenatal ruxolitinib treatment on wild-type C57BL/6 mice, their motor skills, neurobehavioral tests, and electrophysiological properties of hippocampal CA1 neurons during adulthood. Pregnant mice were administered non-toxic doses of ruxolitinib (30 mg/kg/day) orally from E13.5 to E20.5, and nine pups were delivered for each untreated and treated group for downstream analyses. Neurobehavioral and electrophysiological experiments were performed on 8.5–10.5-week-old mice. Administering ruxolitinib prenatally significantly improved muscle strength (p < 0.05). However, no changes were observed in learning ability, motor coordination, locomotor function, exploratory and anxiety-related behaviour, or recognition memory (p > 0.05). Additionally, there were no significant differences in the input/output (IO) function or paired-pulse paradigm in hippocampal CA1 (p > 0.05). In conclusion, prenatal ruxolitinib treatment in C57BL/6 mice shows no adverse effects on behavioral, learning and memory but enhances muscle strength. [ABSTRACT FROM AUTHOR]

Abstract Background Ferroptosis represents a nonapoptotic type of programmed cell death induced by excessive intracellular iron accumulation. Ferroptosis is an essential driver of the pathogenesis of Alzheimer’s disease (AD). Tetrahedral framework nucleic acids (tFNAs) are a novel type of nanoparticle with superior antiapoptotic capacity and excellent biocompatibility. However, the effect of tFNAs on Aβ triggered ferroptosis, cognitive and synaptic impairments in AD remains unknown. Methods N2a cells were treated with Aβ combined with/without tFNAs. Cell viability and levels of Fe2+, lipid peroxidation, MDA, LDH, and GSH were examined. RNA sequencing was applied to explore dysregulated ferroptosis related genes. Seven-month-old APP/PS1 mice were intranasally administrated with tFNAs for two weeks. Fluorescence imaging was used to detect the tFNAs distribution in the brain. Novel object recognition (NOR) test followed by Morris water maze (MWM) was used to test the learning and memory performance of mice. Golgi staining, Western blot, and immunofluorescence staining were used to examine synaptic plasticity. Results tFNAs promoted cell viability and GSH levels, reduced the levels of Fe2+, lipid peroxidation, MDA, and LDH in N2a cells treated with Aβ. RNA sequencing revealed that tFNAs reversed the promotive effect of Aβ on ferroptosis driver Atf3 gene and suppressive effect on ferroptosis suppressors Rrm2 and Furin genes. Fluorescence imaging confirmed the brain infiltration of tFNAs. tFNAs rescued synaptic and memory impairments, and ferroptosis in seven-month-old APP/PS1 mice. Conclusions Collectively, tFNAs inhibited Aβ-mediated ferroptosis and ameliorated cognitive and synaptic impairments in AD mice. tFNAs may serve as novel option to deal with AD. Graphical abstract

Abstract Magnetic fields are widely used in medical diagnostics because of their superior non-invasive properties. In addition, with the widespread use of magnetic fields in transportation and other areas, their potential hazards to human health and the assessment of their safety have attracted considerable attention. The effects of magnetic fields on living organisms have a long history. The biological effects of magnetic field exposure in mice and rats depend on the magnetic field strength, exposure time, and direction; depending on these and potentially other factors, magnetic fields can cause a series of neurobiological effects. We reviewed global research on the neurobiological effects of magnetic fields from recent years to provide an overview and insights into the underlying mechanisms. This review focuses on the biological effects of static and dynamic magnetic fields of different frequencies and intensities on animals and nerve cells and their mechanisms of action.

Although most cognitive impairments induced by prolonged alcohol consumption tend to improve within the initial months of abstinence, there is evidence suggesting certain cognitive deficits may persist. This study aimed to investigate the impact of aerobic exercise on learning and memory in alcohol use disorder (AUD) mice following a period of abstinence from alcohol. We also sought to assess the levels of monoamine neurotransmitters in the hippocampus. To this end, we established an AUD mouse model through a two‐bottle choice (sucrose fading mode and normal mode) and chronic intermittent alcohol vapor (combined with intraperitoneal injection) and randomly allocated mice into exercise groups to undergo treadmill training. Learning and memory abilities were assessed through the Morris water maze test and spontaneous activity was evaluated using the open field test. The levels of dopamine, norepinephrine, serotonin, and brain‐derived neurotrophic factor in the hippocampus were quantified using enzyme‐linked immunoassay (ELISA) kits. The findings reveal that after cessation of alcohol consumption, learning and memory abilities in AUD mice did not completely return to normal levels. The observed enhancement of cognitive functions in AUD mice through aerobic exercise may be attributed to restoring levels of monoamine neurotransmitters in the hippocampus, boosting brain‐derived neurotrophic factor (BDNF) concentrations, and facilitating an increase in hippocampal mass. These results offer empirical evidence to support aerobic exercise as a viable therapeutic strategy to alleviate cognitive deficits associated with AUD.

Neuronal activity is the basis of information encoding and processing in the brain. During neuronal activation, intracellular ATP (adenosine triphosphate) is generated to meet the high-energy demands. Simultaneously, ATP is secreted, increasing the extracellular ATP concentration and acting as a homeostatic messenger that mediates cell–cell communication to prevent aberrant hyperexcitability of the nervous system. In addition to the confined release and fast synaptic signaling of classic neurotransmitters within synaptic clefts, ATP can be released by all brain cells, diffuses widely, and targets different types of purinergic receptors on neurons and glial cells, making it possible to orchestrate brain neuronal activity and participate in various physiological processes, such as sleep and wakefulness, learning and memory, and feeding. Dysregulation of extracellular ATP leads to a destabilizing effect on the neural network, as found in the etiopathology of many psychiatric diseases, including depression, anxiety, schizophrenia, and autism spectrum disorder. In this review, we summarize advances in the understanding of the mechanisms by which extracellular ATP serves as an intercellular signaling molecule to regulate neural activity, with a focus on how it maintains the homeostasis of neural networks. In particular, we also focus on neural activity issues that result from dysregulation of extracellular ATP and propose that aberrant levels of extracellular ATP may play a role in the etiopathology of some psychiatric diseases, highlighting the potential therapeutic targets of ATP signaling in the treatment of these psychiatric diseases. Finally, we suggest potential avenues to further elucidate the role of extracellular ATP in intercellular communication and psychiatric diseases. [ABSTRACT FROM AUTHOR]

Individuals who vary their preferred hand when performing different types of manual activities, so-called mixed handers (MH), have been frequently reported to outperform individuals with a consistent (right) hand preference (cRH) on tasks assessing declarative-memory functions. For example, in one influential study, this MH advantage extended to incidental learning from presumed "deep" semantic processing of verbal stimuli but not from "shallow" phonemic or structural processing. In the present study, we aimed to replicate this research finding in two separate participant samples. First, in a pre-registered and sample-size planned experiment we confronted 49 participants (23 MH; 26 cRH) with "phonemic" and "semantic" word evaluation tasks (using a within design), followed by a surprise delayed recognition test. In a second experiment, we repeated the same procedure with 65 other participants (31 MH, 34 cRH). A mixed-effect analyses of variance found a significant main effect of Encoding Condition (phonemic vs. semantic tasks) in both experiments (effect size: η p 2 =.81 to.85), indicating the classical level-of processing effect with higher recognition hits and sensitivity (d') for words that followed semantic versus phonemic encoding. However, the predicted interaction effect of Encoding Condition with Handedness Group was not statistically significant for either sample (all η p 2 <.03), nor was the main effect of Handedness Group. Thus, our findings conflicted with those of the original study in two independent samples. As we had sufficient statistical power to be confident in our failure to detect a genuine group difference, we cannot confirm the previously reported MH over cRH advantage in incidental learning of verbal material. We discuss possible reasons for these contradictory results and the theoretical implications of this discovery. [ABSTRACT FROM AUTHOR]

Obesity is a significant health concern that is correlated with various adverse health outcomes. Diet-induced obesity (DIO) is associated with impaired cognitive function. Pharmacological treatments for obesity are limited and may have serious adverse effects. Zingiber officinale (ZO) has anti-inflammatory and antioxidant effects, in addition to metabolic effects. This study aimed to assess the effects of Zingiber officinale supplementation on cognitive function, anxiety levels, neurotrophin levels, and the inflammatory and oxidative status in the cortex following DIO in mice. Two-month-old male Swiss mice were fed DIO or standard chow for 4 months and subsequently subdivided into the following groups (n = 10 mice/group): (i) control - vehicle (CNT + vehicle); (ii) CNT supplemented with ZO (CNT + ZO); (iii) obese mice (DIO + vehicle); and (iv) obese mice supplemented with ZO (DIO + ZO) (n = 10). Zingiber officinale extract (400 mg/kg/day) was administered for 35 days via oral gavage. The DIO + vehicle group exhibited impaired recognition memory. The CNT + ZO group presented a greater number of crossings in the open field. No difference between the groups was observed in the plus maze test. DIO + vehicle increased the DCFH and carbonylation levels in the cortex. The DIO + vehicle group presented a reduction in catalase activity. The expression of inflammatory or neurotrophin markers in the cerebral cortex was not different. In conclusion, our findings indicate that supplementation with ZO reverses the cognitive impairment in DIO mice and enhances the antioxidant status of the cerebral cortex. [ABSTRACT FROM AUTHOR]

Prediction error plays a pivotal role in theories of learning, including theories of language acquisition and use. Researchers have investigated whether and under which conditions children, like adults, use prediction to facilitate language comprehension at different levels of linguistic representation. However, many aspects of the reciprocal relation between prediction error and the development of language learning remain unclear. In this article, we review studies in language development that can inform us about the role of prediction error in updating, learning, and retrieving linguistic information. We argue that the study of individual differences in linguistic and cognitive skills will help the field understand more thoroughly whether, when, and why prediction aids language learning, and whether prediction error necessarily results in language learning and retrieval from memory. We close with a discussion of the needs and challenges for researchers to answer these questions. [ABSTRACT FROM AUTHOR]

Background and purpose: Stress, especially immobility stress, is quite common and one of the most important and influential risk factors in neurological disorders. This study aimed to investigate the effect of acute and chronic immobility stress on the level of cortical and hippocampal oxidative stress indicators and memory impairment following global cerebral ischemia. Experimental approach: In this study, 48 male Wistar rats were randomly divided into 6 groups: 1, sham (S); 2, sham-acute stress (SSA); 3, sham-chronic stress (SSC); 4, ischemia (IS); 5, ischemia-acute stress (ISA); 6, ischemia-chronic stress (ISC). The Morris water maze (MWM) test was performed 14 days after surgery, and cortisol levels and oxidative stress factors such as malondialdehyde MDA and total thiol were measured. Findings/Results: In the MWM test, the time to find the platform (latency time) in the ISC and IS groups significantly increased compared to the S group. The time spent in the target quarter in these two groups was significantly reduced compared to the S group on the day of the probe. The results showed a significant increase in cortisol levels and malondialdehyde concentration in the ISA, ISC, and IS groups compared to the S group, but there was no significant difference in total thiol concentration. No significant difference was observed in the level of oxidative stress factors in the cortex. Conclusion and implication: Chronic immobility stress could reduce antioxidant factors in the hippocampus and exacerbate memory impairment caused by global ischemia.

Abstract Background The impact of acrylamide (ACR) on learning and memory has garnered considerable attention. However, the targets and mechanisms are still unclear. Results Elongation factor 2 (eEF2) was significantly upregulated in the results of serum proteomics. Results from in vitro and in vivo experiments indicated a notable upregulation of Eukaryotic elongation factor 2 kinase (eEF2K), the sole kinase responsible for eEF2 phosphorylation, following exposure to ACR (P

Abstract Background We recently reported that the dopamine (DA) analogue CA140 modulates neuroinflammatory responses in lipopolysaccharide-injected wild-type (WT) mice and in 3-month-old 5xFAD mice, a model of Alzheimer’s disease (AD). However, the effects of CA140 on Aβ/tau pathology and synaptic/cognitive function and its molecular mechanisms of action are unknown. Methods To investigate the effects of CA140 on cognitive and synaptic function and AD pathology, 3-month-old WT mice or 8-month-old (aged) 5xFAD mice were injected with vehicle (10% DMSO) or CA140 (30 mg/kg, i.p.) daily for 10, 14, or 17 days. Behavioral tests, ELISA, electrophysiology, RNA sequencing, real-time PCR, Golgi staining, immunofluorescence staining, and western blotting were conducted. Results In aged 5xFAD mice, a model of AD pathology, CA140 treatment significantly reduced Aβ/tau fibrillation, Aβ plaque number, tau hyperphosphorylation, and neuroinflammation by inhibiting NLRP3 activation. In addition, CA140 treatment downregulated the expression of cxcl10, a marker of AD-associated reactive astrocytes (RAs), and c1qa, a marker of the interaction of RAs with disease-associated microglia (DAMs) in 5xFAD mice. CA140 treatment also suppressed the mRNA levels of s100β and cxcl10, markers of AD-associated RAs, in primary astrocytes from 5xFAD mice. In primary microglial cells from 5xFAD mice, CA140 treatment increased the mRNA levels of markers of homeostatic microglia (cx3cr1 and p2ry12) and decreased the mRNA levels of a marker of proliferative region-associated microglia (gpnmb) and a marker of lipid-droplet-accumulating microglia (cln3). Importantly, CA140 treatment rescued scopolamine (SCO)-mediated deficits in long-term memory, dendritic spine number, and LTP impairment. In aged 5xFAD mice, these effects of CA140 treatment on cognitive/synaptic function and AD pathology were regulated by dopamine D1 receptor (DRD1)/Elk1 signaling. In primary hippocampal neurons and WT mice, CA140 treatment promoted long-term memory and dendritic spine formation via effects on DRD1/CaMKIIα and/or ERK signaling. Conclusions Our results indicate that CA140 improves neuronal/synaptic/cognitive function and ameliorates Aβ/tau pathology and neuroinflammation by modulating DRD1 signaling in primary hippocampal neurons, primary astrocytes/microglia, WT mice, and aged 5xFAD mice.

Abstract Recent years, the rapid advancement of technology has raised concerns. We studied the effects of prenatal exposure to 900 MHz radiofrequency (RF) from mobile phones and the protective effects of linalool on learning and memory, and anxiety in adolescent male and female offspring rats. Pregnant rats were divided into four groups: control, wave, wave + linalool, and linalool. Rats received linalool (25mg/kg) by gavage for 21 days. Irradiation was conducted from day 0 to day 21 of pregnancy. Offsprings underwent behavioral and electrophysiological tests on days 50 and 60 after birth. Exposure to RF during pregnancy caused anxiety-like behavior in the EPM test and impairment of learning and memory in the Morris water maze and shuttle box tests. Electrophysiological properties and synaptic plasticity of the dorsal hippocampal CA3-CA1 synapse showed a decrease in fEPSP amplitude and slope. The trace element levels in both male and female offspring were consistent across all groups compared to their respective controls. In the hippocampus tissue, the levels of Fe, Cu, and Mn, as well as the Cu/Zn ratio, were significantly higher in the exposed groups (wave groups) compared to their controls. Moreover, Zn levels were significantly lower in the hippocampus tissue of the exposed groups. Linalool administration mitigated the excessive increase in Fe, Cu, Mn, and Cu/Zn ratio and normalized the disrupted levels of trace elements, except for Zn levels in both male and female offspring. Sex differences were observed in the EPM and shuttle box tests, females were more sensitive than males. In summary, our study demonstrates that prenatal exposure to mobile phone radiation induces stress-like behaviors, disrupts learning and memory, alters hippocampal electrophysiological properties and trace element balance in offspring. Treatment with linalool mitigates these deleterious effects, highlighting its potential as a therapeutic intervention. These findings contribute to our understanding of the impact of prenatal environmental exposures on neurodevelopment and offer insights into potential strategies for neuroprotection.

Emotions, in general, have no scientific definition. Emotions can be denoted as the mental state because of the neurophysiological changes. Emotions are related to mood, personality, temperament, and consciousness. People exhibit different emotions in different situations causing changes in cognitive functions. One of the major cognitive functions is the ability to learn, to store the acquired information in the parts of the brain such as the hippocampus, amygdala, cortex, and cerebellum. Learning and memory are affected by different types of emotions. Emotional responses such as fear, depression, and stress have impaired effects on cognitive functions such as learning and memory, whereas optimistic and happy emotions have positive effects on long-term memory. Certain disorders have greater effects on the regions of the brain which are also associated with synaptic plasticity and Learning and Memory(LM). Neuroimaging techniques are involved in studying the changing regions of the brain due to varied emotions and treatment strategies based on the changes observed. There are many drugs, and in advancements, nanotechnology is also utilized in the treatment of such psychiatric disorders. To improve mental health and physical health, emotional balance is most important, and effective care should be provided for people with less emotional quotient and different types of disorders to inhibit cognitive dysfunctions. In this review, emotions and their varied effects on a cognitive function named learning and memory, disorders associated with the defects of learning due to emotional instability, the areas of the brain that are in control of emotions, diagnosis, and treatment strategies for psychiatric disorders dependent on emotions are discussed.

Background: The impact of acrylamide (ACR) on learning and memory has garnered considerable attention. However, the targets and mechanisms are still unclear. Results: Elongation factor 2 (eEF2) was significantly upregulated in the results of serum proteomics. Results from in vitro and in vivo experiments indicated a notable upregulation of Eukaryotic elongation factor 2 kinase (eEF2K), the sole kinase responsible for eEF2 phosphorylation, following exposure to ACR (P < 0.05). Subsequent in vitro experiments using eEF2K siRNA and in vivo experiments with eEF2K-knockout mice demonstrated significant improvements in abnormal indicators related to ACR-induced learning and memory deficits (P < 0.05). Proteomic analysis of the hippocampus revealed Lpcat1 as a crucial downstream protein regulated by eEF2K. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that eEF2K may play a role in the process of ACR-induced learning and memory impairment by affecting ether lipid metabolism. Conclusions: In summary, eEF2K as a pivotal treatment target in the mechanisms underlying ACR-induced learning and memory impairment, and studies have shown that it provides robust evidence for potential clinical interventions targeting ACR-induced impairments. [ABSTRACT FROM AUTHOR]

A topic of recent debate is the hypothesis that deficits associated with developmental disorders of language, such as reading disability, can be explained by a selective weakness in procedural memory. Adults with (n = 29; RD) and without (n = 29; TD) reading disability completed a weather prediction task under immediate and delayed feedback conditions, that rely on the striatal (procedural) and hippocampal (declarative) circuits, respectively. We examined trial‐by‐trial accuracy by feedback condition (immediate vs. delayed) and group (RD vs. TD). In the immediate feedback condition, we found the TD group to have a higher learning rate than the RD group. In the delayed feedback condition, we found the TD group reach a high level of accuracy early, and outperform the RD group for the duration of the task. The TD group also made gains in reaction time under both conditions, while the RD group slowed in their responses. Taken together, it appears that while procedural memory is indeed impaired in adults with reading disability, to a lesser extent, declarative memory is also affected. This lends partial support to the PDH, and more broadly to the position that reading disability is associated with general (non‐linguistic) difficulties in learning. [ABSTRACT FROM AUTHOR]

Phenylacetaldehyde (PAH), an aromatic compound, is present in a diverse range of fruits including overripe bananas and prickly pear cactus, the two major host fruits for Drosophila melanogaster. PAH acts as a potent ligand for the ionotropic receptor 84a (IR84a) in the adult fruit fly and it is detected by the IR84a/IR8a heterotetrameric complex. Its role in the male courtship behavior through IR84a as an environmental aphrodisiac is of additional importance. In D. melanogaster, two distinct kinds of olfactory receptors, that is, odorant receptors (ORs) and ionotropic receptors (IRs), perceive the odorant stimuli. They display unique structural, molecular, and functional characteristics in addition to having different evolutionary origins. Traditionally, olfactory cues detected by the ORs such as ethyl acetate, 1‐butanol, isoamyl acetate, 1‐octanol, 4‐methylcyclohexanol, etc. classified as aliphatic esters and alcohols have been employed in olfactory classical conditioning using fruit flies. This underlines the participation of OR‐activated olfactory pathways in learning and memory formation. Our study elucidates that likewise ethyl acetate (EA) (an OR‐responsive odorant), PAH (an IR‐responsive aromatic compound) too can form learning and memory when associated with an appetitive gustatory reinforcer. The association of PAH with sucrose (PAH/SUC) led to learning and formation of the long‐term memory (LTM). Additionally, the Orco1, Ir84aMI00501, and Ir8a1 mutant flies were used to confirm the exclusive participation of the IR84a/IR8a complex in PAH/SUC olfactory associative conditioning. These results highlight the involvement of IRs via an IR‐activated pathway in facilitating robust olfactory behavior. [ABSTRACT FROM AUTHOR]

Objective：To observe the effects of repetitive transcranial magnetic stimulation (rTMS) at different frequencies on learning and memory abilities in rats during the early recovery phase of middle cerebral artery occlusion (MCAO) and to explore the underlying mechanisms. Method： Successfully modelled MCAO rats were randomly divided into the model group, low- frequency group, high- frequency group, and sham- operated group was set up at the same time, with 12 rats in each group. The low-frequency group and high-frequency group were stimulated with a CCY-I transcranial magnetic stimulator 2 times/day for 14d; the low-frequency group was treated with 1Hz at the left prefrontal lobe of the rat's skull, and the high-frequency group was treated with 10Hz at the right prefrontal lobe. The model group and the sham-operated group were not treated but were subjected to the same conditions of handling and restraint before returning to their cages. Neurobehavioral scores were recorded on the 1st and 14th day after the operation; the Morris water maze test was conducted on day 3—7 after the operation; TTC staining, PCR and Western blot to detect the mRNA and protein expression of key genes (Notch1, Hes1, Hes5) were performed at the end of the intervention on the 14th postoperative day. Result：①Neurological deficit scores: After 14 days of intervention, both the high-frequency and low-frequency groups showed a reduction in neurofunctional compared to the model group (P<0.05), with no significant difference between the model group and high-frequency group (P>0.05). ②Morris water maze experiment: The average escape latency during the directional navigation experiment was significantly reduced day by day in the low frequency group, high frequency group and sham operation group (P<0.05). The escape latency was shorter in the high- frequency group compared to the model group, and shorter in the low- frequency group compared to the high-frequency group (P<0.05). The number of platform crossings in the spatial exploration experiment showed no significant difference between low frequency group and sham operation group, high frequency group and model group (P>0.05). The high-frequency group and the model group had fewer crossing than the sham operation group, and the low-frequency group had more than the model group and high-frequency group (P<0.05). ③TTC staining: The infarct size in the low-frequency group and high-frequency group was significantly smaller than in the model group. ④PCR and Western blot: Compared to the model group, the high frequency group and the low frequency group had significantly increased mRNA and protein expression of Notch1, Hes1 and Hes5 (P<0.05). There was no significant difference in the mRNA and protein expression of Notch1, Hes1 and Hes5 between the low frequency group and high frequency group (P>0.05). Conclusion： Both high and low frequency rTMS can improve the learning and memory abilities in MCAO rats, potentially by activating and increasing the expression of the Notch1 pathway in hippocampal tissues, which improves the synaptic plasticity of hippocampus. [ABSTRACT FROM AUTHOR]

Objective: Ethanol (Eth) intake is known to cause numerous detrimental effects on the structure and function of the brain, and it is commonly used as a psychostimulant drug by adolescents. Conversely, omega‐3 (O3) can reduce the risk of cognitive decline and promote the maintenance of neurophysiological functions. In this study, we investigated the protective effects of O3 on behavioral alterations, oxidative stress, and interleukin‐6 (IL‐6) levels induced by chronic Eth intake during adolescence in rats. Materials and methods: Adolescent male rats (21 days old) were divided as follows: (1) Vehicle, (2) Eth (Eth in drinking water [20%]), (3–5) Eth + O3 (50/100/150 mg/kg), and (6) O3 (150 mg/kg). After 5 weeks, Morris water maze (MWM) and passive avoidance (PA) tests were performed, and the hippocampal and cortical levels of oxidative stress markers and inflammatory indices were measured. Results: Adolescent Eth intake impairs learning and memory function in MWM and PA tests (groups × day, p < 0.05 and p < 0.001, respectively). It was shown that Eth induced oxidative stress and neuroinflammation. O3 improved learning and impairment induced by Eth by reducing the adverse effects of Eth on the oxidant/antioxidant balance in the hippocampi (for malondialdehyde [MDA]/thiol: p < 0.01, p < 0.001, respectively) and for superoxide dismutase (SOD)/catalase (CAT): p < 0.01 and p < 0.05, respectively). Furthermore, we found that O3 prevented the Eth‐induced increase of hippocampal IL‐6 (p < 0.001). Conclusion: O3 supplementation acts as an effective approach to prevent learning and memory impairments induced by chronic Eth consumption during adolescence. In this respect, the antioxidant and anti‐inflammatory properties of O3 seem to be the main underlying mechanisms of neuroprotection. [ABSTRACT FROM AUTHOR]

Simple Summary: This perspective article examines the differences between memory, information, and knowledge. It is proposed that the creation of knowledge is not simply the extraction of information or sequencing and storage of memories, but its contextualization that offers a point of advantage for survival within a decision-making framework; outside these contexts there are no useful memories and therefore no relevant knowledge. A constellation of neural networks spread across multiple brain regions must work together to grow knowledge over time. Knowledge must be stored in such a way that it can be accessed by multiple tokens, or handles, at any time. The emergence of knowledge networks underlies the evolution of complex brains that can predict outcomes, induce imagination and expand knowledge. Attention and sleep play important roles in creating and protecting knowledge. The brain receives information via sensory inputs through the peripheral nervous system and stores a small subset as memories within the central nervous system. Short-term, working memory is present in the hippocampus whereas long-term memories are distributed within neural networks throughout the brain. Elegant studies on the mechanisms for memory storage and the neuroeconomic formulation of human decision making have been recognized with Nobel Prizes in Physiology or Medicine and in Economics, respectively. There is a wide gap, however, in our understanding of how memories of disparate bits of information translate into "knowledge", and the neural mechanisms by which knowledge is used to make decisions. I propose that the conceptualization of a "knowledge network" for the creation, storage and recall of knowledge is critical to start bridging this gap. Knowledge creation involves value-driven contextualization of memories through cross-validation via certainty-seeking behaviors, including rumination or reflection. Knowledge recall, like memory, may occur via oscillatory activity that dynamically links multiple networks. These networks may show correlated activity and interactivity despite their presence within widely separated regions of the nervous system, including the brainstem, spinal cord and gut. The hippocampal–amygdala complex together with the entorhinal and prefrontal cortices are likely components of multiple knowledge networks since they participate in the contextual recall of memories and action selection. Sleep and reflection processes and attentional mechanisms mediated by the habenula are expected to play a key role in knowledge creation and consolidation. Unlike a straightforward test of memory, determining the loci and mechanisms for the storage and recall of knowledge requires the implementation of a naturalistic decision-making paradigm. By formalizing a neuroscientific concept of knowledge networks, we can experimentally test their functionality by recording large-scale neural activity during decision making in awake, naturally behaving animals. These types of studies are difficult but important also for advancing knowledge-driven as opposed to big data-driven models of artificial intelligence. A knowledge network-driven understanding of brain function may have practical implications in other spheres, such as education and the treatment of mental disorders. [ABSTRACT FROM AUTHOR]

Exercise has been recognized as a beneficial factor for cognitive health, particularly in relation to the hippocampus, a vital brain region responsible for learning and memory. Previous research has demonstrated that exercise-mediated improvement of learning and memory in humans and rodents correlates with increased adult neurogenesis and processes related to enhanced synaptic plasticity. Nevertheless, the underlying molecular mechanisms are not fully understood. With the aim to further elucidate these mechanisms, we provide a comprehensive dataset of the mouse hippocampal transcriptome at the single-cell level after 4 weeks of voluntary wheel-running. Our analysis provides a number of interesting observations. For example, the results suggest that exercise affects adult neurogenesis by accelerating the maturation of a subpopulation of Prdm16-expressing neurons. Moreover, we uncover the existence of an intricate crosstalk among multiple vital signaling pathways such as NF-κB, Wnt/β-catenin, Notch, and retinoic acid (RA) pathways altered upon exercise in a specific cluster of excitatory neurons within the Cornu Ammonis (CA) region of the hippocampus. In conclusion, our study provides an important resource dataset and sheds further light on the molecular changes induced by exercise in the hippocampus. These findings have implications for developing targeted interventions aimed at optimizing cognitive health and preventing age-related cognitive decline. [ABSTRACT FROM AUTHOR]

Short- and long-term forms of N-methyl-d-aspartate receptor (NMDAR)-dependent potentiation (most commonly termed short-term potentiation (STP) and long-term potentiation (LTP)) are co-induced in hippocampal slices by theta-burst stimulation, which mimics naturally occurring patterns of neuronal activity. While NMDAR-dependent LTP (NMDAR-LTP) is said to be the cellular correlate of long-term memory storage, NMDAR-dependent STP (NMDAR-STP) is thought to underlie the encoding of shorter-lasting memories. The mechanisms of NMDAR-LTP have been researched much more extensively than those of NMDAR-STP, which is characterized by its extreme stimulation dependence. Thus, in the absence of low-frequency test stimulation, which is used to test the magnitude of potentiation, NMDAR-STP does not decline until the stimulation is resumed. NMDAR-STP represents, therefore, an inverse variant of Hebbian synaptic plasticity, illustrating that inactive synapses can retain their strength unchanged until they become active again. The mechanisms, by which NMDAR-STP is stored in synapses without a decrement, are unknown and we report here that activation of metabotropic glutamate receptors may be critical in maintaining the potentiated state of synaptic transmission. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'. [ABSTRACT FROM AUTHOR]

Hippocampal long-term potentiation (LTP) and long-term depression (LTD) are Hebbian forms of synaptic plasticity that are widely believed to comprise the physiological correlates of associative learning. They comprise a persistent, input-specific increase or decrease, respectively, in synaptic efficacy that, in rodents, can be followed for days and weeks in vivo. Persistent (>24 h) LTP and LTD exhibit distinct frequency-dependencies and molecular profiles in the hippocampal subfields. Moreover, causal and genetic studies in behaving rodents indicate that both LTP and LTD fulfil specific and complementary roles in the acquisition and retention of spatial memory. LTP is likely to be responsible for the generation of a record of spatial experience, which may serve as an associative schema that can be re-used to expedite or facilitate subsequent learning. In contrast, LTD may enable modification and dynamic updating of this representation, such that detailed spatial content information is included and the schema is rendered unique and distinguishable from other similar representations. Together, LTP and LTD engage in a dynamic interplay that supports the generation of complex associative memories that are resistant to generalization. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'. [ABSTRACT FROM AUTHOR]

The integrated stress response (ISR), a pivotal protein homeostasis network, plays a critical role in the formation of long-term memory (LTM). The precise mechanism by which the ISR controls LTM is not well understood. Here, we report insights into how the ISR modulates the mnemonic process by using targeted deletion of the activating transcription factor 4 (ATF4), a key downstream effector of the ISR, in various neuronal and non-neuronal cell types. We found that the removal of ATF4 from forebrain excitatory neurons (but not from inhibitory neurons, cholinergic neurons, or astrocytes) enhances LTM formation. Furthermore, the deletion of ATF4 in excitatory neurons lowers the threshold for the induction of long-term potentiation, a cellular model for LTM. Transcriptomic and proteomic analyses revealed that ATF4 deletion in excitatory neurons leads to upregulation of components of oxidative phosphorylation pathways, which are critical for ATP production. Thus, we conclude that ATF4 functions as a memory repressor selectively within excitatory neurons. [ABSTRACT FROM AUTHOR]

• PI3K/Akt signaling pathway is related to anti-apoptosis and pro-axonal regeneration. • The PI3K/Akt pathway is a potential key pathway for the treatment of PSCI in TCM. • Moxibustion can activate the PI3K/Akt signaling pathway to function. • Moxibustion can promote axonal regeneration and improve learning and memory of PSCI. This study aimed to investigate whether moxibustion could affect PI3K/Akt pathway to regulate Transforming acidic coiled-coil containing protein 3 (TACC3) and promote axonal regeneration to improve learning and memory function in middle cerebral artery occlusion (MCAO) rats. Sixty SD rats were randomly divided into 4 groups: sham-operated control group (SC), model control group (MC), model + moxibustion group (MM), and model + inhibitor + moxibustion group (MIM). The rats in MC, MM, and MIM groups were made into MCAO models, and PI3K inhibitor LY294002 was injected into the rats in MIM group before modeling; while the rats in SC group were only treated with artery separation without monofilament inserting. After that, the rats in MM and MIM groups were intervented with moxibustion. We used the Zea-Longa scale, micro-Magnetic Resonance Imaging (micro-MRI), Morris water maze (MWM), TUNEL, western blot (WB), immunofluorescence and immunohistochemistry to evaluate the neurological deficits, cerebral infarct volume, learning and memory, apoptotic cell percentage in the hippocampal, the expression level of axonal regeneration and PI3K/AKt related proteins, the expression level of TACC3. The detection of 2 h after surgery showed the result before moxibustion and 7 days after the intervention showed the results after moxibustion. After 7 d of intervention, the scores of Zea-Longa and the cerebral infarct volume, the escape latency, the percentage of apoptosis cells of MM group were lower than that of MC and MIM groups; the frequency of rats crossed the previous platform location, PI3K, p-Akt/t-Akt and TACC3, the level of GAP-43 in MM group was more than MC and MIM groups (P < 0.05). While no statistical difference existed between MIM group and MC group (P > 0.05). Moxibustion can promote axonal regeneration and improve learning and memory of Post-stroke cognitive impairment via activating the PI3K/AKT signaling pathway and TACC3. [ABSTRACT FROM AUTHOR]