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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.

Maintaining GABAergic inhibition within physiological limits in the medial prefrontal cortex (mPFC) is critical for working memory. While synaptic GABAAR typically mediate the primary component of mPFC inhibition, the role of extrasynaptic δ-GABAAR in working memory remains unclear. To investigate this, we used fiber photometry to examine the effects of δ-GABAAR in freely moving mice. Our results indicate that the loss of δ-GABAAR expression leads to learning and memory impairment. Specifically, activation of δ-GABAAR impaired learning and memory in WT mice but enhanced learning and memory in δ+/− knockout mice. Furthermore, δ-GABAAR activation increased calcium activity in the mPFC pyramidal neurons, an effect not observed in δ-Cas9-sgRNA virus-infected mice. Collectively, these findings suggest that δ-GABAAR deficiency impairs learning and memory by modulating the excitability of pyramidal neurons in the mPFC. These results delineate the functional contribution of δ-GABAAR to learning and memory, suggesting their role extends beyond the mere maintenance of information. [ABSTRACT FROM AUTHOR]

Recent studies highlight the role of brain metabolites in regulation of neuronal signals and behaviour. To understand the underlying mechanism, brain metabolites and associated signaling molecules were examined in early adolescent rat experienced CRS. Rats were tested for their learning and memory ability, and their metabolite profile was evaluated using Gas chromatography-mass spectrometry (GC-MS). Differences in metabolites were examined by variable importance in projection (VIP) and multivariate analysis. Ingenuity Pathway Analysis (IPA) and KEGG ID were performed for the identified metabolites. We found that CRS altered the metabolites that were involved in biosynthesis of steroid hormone, aminoacyl t-RNA, L-Dopa biosynthesis, and metabolism of tyrosine, fatty acid, and purine. Further analysis showed reduction of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR, a metabolite involved in purine metabolism) an AMP kinase activator, influenced the hypoxanthine-guanine phosphoribosyltransferase (HPRT), serotonin transporter (SERT), postsynaptic density protein (PSD) -95, its phosphorylation and brain-derived neurotrophic factor (BDNF) in CRS animals, which displayed deficit in memory. The AICAR treated CRS rats showed improved memory and altered metabolites and other molecules (HPRT, SERT, PSD-95 and BDNF) levels were restored. Our analysis revealed that CRS induced changes in metabolites possibly altered synaptic plasticity and memory in which HPRT, SERT-PSD95-BDNF associated pathway involved. Taken together, our observation provides initial insight into how stress differently influences the metabolic pathway, and associated behaviour. Further study will help to develop pharmacological intervention strategies. [ABSTRACT FROM AUTHOR]

In recent years, the influence of dietary-related factors on neurodegenerative diseases has received considerable attention in the academic community, notably involving the food additive sodium nitrite (NaNO2) and intermittent fasting behavior. However, the effects of NaNO2 and intermittent fasting on spatial learning and memory have not been thoroughly investigated. This study conducted a controlled experiment to explore the impact of NaNO2 and intermittent fasting on the hyperphosphorylation of hippocampal neurofilament (NF) and tau proteins, as well as spatial learning and memory in rats. Through Morris water maze experiments, the spatial learning and memory abilities of rats were assessed, while immunoblotting and immunohistochemistry techniques were employed to evaluate the phosphorylation levels and distribution of NF and tau proteins in the rat hippocampus. NaNO2 was found to induce hyperphosphorylation of hippocampal NF and tau proteins at the Ser396/404 sites, which was accompanied by a decline in spatial learning and memory abilities. Conversely, intermittent fasting ameliorated the NaNO2-induced hyperphosphorylation of hippocampal neurofilaments and the decline in learning and memory abilities, with no discernible effect on hippocampal tau protein hyperphosphorylation. [ABSTRACT FROM AUTHOR]

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]

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Background/Objectives: We assessed the influence of long-term injection of magnoflorine (MAG) on memory acquisition in mice for the first time. Methods: This isoquinoline alkaloid that belongs to the aporphines was isolated from the roots of Berberis vulgaris by centrifugal partition chromatography (CPC) using a biphasic solvent system composed of chloroform: methanol: water in the ratio 4:3:3 (v/v/v) with 20 mM of hydrochloric acid and triethylamine, within 64 min. Results: Our results indicated that long-term injection of MAG 20 mg/kg dose improve the long-term memory acquisition in mice that were evaluated in the passive avoidance (PA) test with no toxicity records. The analysis of brain lysates and animal plasma by HPLC-ESI-QTOF-MS/MS showed the ability of the compound to cross the blood–brain barrier, and an elevated level of phosphatidylcholine PC (14:1(9Z)/14:1(9Z)) with the molecular formula of C36H69NO8P was observed in both treated groups with 10 mg/kg and 20 mg/kg MAG in comparison to the control group. Conclusions: This phenomenon may explain MAG's cognition-enhancing properties as the PC may induce the synthesis and strengthening of neuronal cells. Also, the 7-day-long administration of MAG at 10 mg/kg and 20 mg/kg increased the mean number of parvalbumin (PV)-IR neurons in the hippocampus. Statistically, the largest PV-IR neurons were observed at the 20 mg/kg dose, which may indicate a potential effect of MAG on Ca2+ metabolism. However, no statistical differences were observed in the mean number of PV-IR nerve fibers in both doses of MAG, regardless of the hippocampal fields. This positive effect of MAG on hippocampal neurons provides further support for the neuroprotective effect of this alkaloid. [ABSTRACT FROM AUTHOR]

Previous studies have indicated that the infralimbic (IL) and prelimbic (PL) subdivisions of the medial prefrontal cortex (mPFC) serve as critical modulators of fear suppression and expression. Although significant research has been conducted on the extinction of conditioned fear, the mechanisms underlying contextual fear discrimination learning, a form of contingency judgment learning, remain inadequately understood. Our investigation aimed to explore the influence of epigenetic regulation associated with cyclic AMP-response element binding protein (CREB)-dependent long-term memory encoding within the IL and PL on contextual fear discrimination. Our prior and current findings illustrate that epigenetic hypofunction induced by a CREB-Binding Protein (CBP) mutant, which is deficient in histone acetyltransferase activity (CBPΔHAT), within the mPFC leads to compromised contextual fear discrimination while not affecting contextual fear conditioning in these mutants. Unexpectedly, the effect was not noticeable when the hypofunction was constrained to the infralimbic (IL) area; however, the hypofunction of the prelimbic (PL) network led to considerable impairment in fear discrimination. The findings indicate that learning fear discrimination involves differential encoding across the specialized networks of the mPFC. These data suggest that the IL network is not essential for encoding during the acquisition and discrimination of fear or that the PL network may compensate for the IL's inability to encode new information. Furthermore, these results emphasize the importance of histone acetylation in the mPFC as a crucial physiological mechanism for learning contingency judgment. [ABSTRACT FROM AUTHOR]

The zebrafish (Danio rerio) model is increasingly popular in neurobehavioral research, and behavioral outcomes are commonly evaluated in studies on neurodegeneration and neurotoxicity. Sex and age have been identified as important variables in cognition studies; however, these factors are often underreported in published studies that use the zebrafish model, leading to uncertainty about their impact in zebrafish T‐maze experiments. In this study, we evaluated the role of sex and age in zebrafish cognitive function using a 5‐day T‐maze task. Our results demonstrated that female and younger zebrafish had increased learning and memory capacity. These findings highlighted the importance of considering and reporting sex and age in experimental design in zebrafish cognitive neurobehavioral studies. [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]

Background: Alzheimer's disease (AD) as a neurodegenerative disease can cause behavioral impairments due to oxidative stress. Aging and oxidative conditions are some AD risk factors. Objective: We assessed the influence of geraniol (GR), an acyclic monoterpene alcohol, on behavioral functions, hippocampal oxidative status, and histological alterations in AD rats induced by amyloid-β (Aβ). Methods: Male Wistar rats (n = 70) were randomly allocated to the control, sham, AD, control-GR (100 mg/kg; per oral: P.O.), AD-GR (100 mg/kg; P.O.; treatment), GR-AD (100 mg/kg; P.O.; pretreatment), and GR-AD-GR (100 mg/kg; P.O.; pretreatment + treatment) groups. GR administration was done for four continuous weeks. After treatments, novel object recognition (NOR) and Morris water maze (MWM) tests assessed the animals' behavior. Then, hippocampal specimens were collected for biochemical assessment. Finally, the number of intact neurons was identified in the hippocampus using hematoxylin and eosin staining. Results: Aβ microinjection increased learning and memory deficits in both NOR and MWM tests, oxidative stress status, and neuronal loss. Oral GR administration improved behavioral deficits and reduced oxidative stress status and neuronal loss in the Aβ-infused animals. Conclusions: GR ameliorates behavioral impairments through a decrease in neuronal degeneration and oxidative stress. [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]

Infants born with intrauterine growth restriction (IUGR) have up to a five-fold higher risk of learning and memory impairment than those with normal growth. Using a mouse model of hypertensive diseases of pregnancy (HDP) to replicate uteroplacental insufficiency (UPI), we have previously shown that UPI causes premature embryonic hippocampal dentate gyrus (DG) neurogenesis in IUGR offspring. The DG is a brain region that receives the first cortical information for memory formation. In the current study, we examined the postnatal DG neuron morphology one month after delivery (P28) using recombinant adeno-associated viral labeling of neurons. We also examined DG microglia's morphology using immunofluorescent histochemistry and defined the hippocampal cytokine/chemokine milieu using Luminex xMAP technology. We found that IUGR preserved the principal dendrite lengths but decreased the dendritic branching and volume of DG neurons. IUGR augmented DG microglial number and cell size. Lastly, IUGR altered the hippocampal cytokine/chemokine profile in a sex-specific manner. We conclude that the prematurely-generated neuronal progenitors develop abnormal morphologies postnatally in a cell-autonomous manner. Microglia appear to modulate neuronal morphology by interacting with dendrites amidst a complex cytokine/chemokine environment that could ultimately lead to adult learning and memory deficits in our mouse model. [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]

Background: Masticatory dysfunction and periodontitis are independently linked to cognitive decline. This article aims to highlight the individual and common roles that periodontitis and tooth loss play in cognition. Specifically, we aim to summarize the behavioral effects on learning and memory that result from each pathology, explore mechanisms that may explain these effects, and review the commonalities between the two. Methods: The PubMed database was used to implement searches of relevant clinical studies on the correlations between edentulism and cognitive decline as well as periodontitis and cognitive decline. Additional searches were done to investigate animal studies that provided behavioral and mechanistic findings to explain these relationships. The clinical and animal studies were summarized and analyzed in this review to reveal the commonalities and differences between these comorbidities. Results: The clinical studies summarized in this review report significant correlations between both periodontitis and partial/full edentulism with cognitive decline. The behavioral and mechanistic findings in animal model studies are summarized to support the cognitive effects. Both in vivo and in vitro studies have identified key pathogens, molecules, or cellular pathways that contribute to a more comprehensive understanding of the pathophysiologic processes that link different types of oral disease to cognitive brain function. Practical Implications: The correlation between oral disease and cognitive impairment has been well established but further exploration of the molecular and cellular mechanisms underlying these relationships can provide therapeutic implications and stress the importance of oral health and preventative care. Abbreviations AD: Alzheimer's Disease; AFT: animal fluency test; BOP: bleeding on probing; BGI: biofilm-gingival interface; CAL: clinical attachment loss; CDT: clock drawing test; CERAD: Consortium to Establish a Registry for Alzheimer's Disease word learning test; CNS: central nervous system; CP: chronic periodontitis; DSST: digital substitution test; IL-1β: interleukin 1β; IL-6: interleukin 6; LC: locus coeruleus; MMP: matrix metalloproteinase; MMSE: Mini-Mental Status Examination; MoCA: Montreal Cognitive Assessment; MRI: Magnetic Resonance Imaging; MWM: Morris water maze; NO: nitric oxide; PDL: periodontal ligament; PISA: periodontal inflamed surface area; PP2A: protein phosphatase 2A; RABL: radiographic alveolar bone loss; RANKL: Receptor activator of nuclear factor-κB ligand; SCT: spatial copying task; TLR4: toll-like receptor 4; TNF-α: tumor necrosis factor α; Vmes: Mesencephalic trigeminal nucleus. [ABSTRACT FROM AUTHOR]

To investigate the differences in the ability of egg yolk lipids to alleviate the decline in learning and cognitive abilities in mice under different temperature treatments. This study utilized a mouse model of cognitive impairment to compare the varying impacts on learning and cognitive functions resulting from 95 ℃ (30 min in water bath) and 121 ℃ (30 min in sterilization pot) heat treatments of egg yolk lipid components. The research results showed that compared with 121 ℃ heat treatment of egg yolk lipids, 95 ℃ heat treatment of egg yolk lipids effectively reduced the phosphorylation of Tau protein and the expression of Aβ1-40 and GSK-3β, downregulated the expression of pro-inflammatory factors, and had a better effect on improving the learning and memory abilities of mice. The levels of polyunsaturated fatty acids and DHA in 95 ℃ heat treatment of egg yolk lipids were significantly increased compared to those treated at 121 ℃ (P

BackgroundCyclic AMP response element binding protein (CREB) and miR-132-3p have been proved to be related to many neurodegenerative diseases. Our research group previously has demostrated that the neurotoxicity of aluminum is relevant to abnormal phosphorylation of tau protein, but whether aluminum affects the abnormal phosphorylation of tau protein through GREB and miR-132-3p has not been reported yet .ObjectiveTo investigate the effect of aluminum on CREB and miR-132-3p during abnormal phosphorylation of tau protein in rat hippocampus.MethodsTwenty-eight two-month-old SD rats with comparable weigh, were randomly assigned to four groups: control group (saline) and low, middle, and high dose exposure groups [10, 20, and 40 μmol·kg−1 Al(mal)3] with each group containing 7 rats, and the exposure period was 3 months by intraperitoneal injection every other day. After rats’ exposure to aluminum, Morris water maze was employed to assess their capabilities of learning and memory. The miR-132-3p gene expression level was detected by quantitative real-time PCR (qRT-PCR). The levels of CREB, phosphorylated CREB (p-CREB) (Ser133), RAS p21 protein activator 1 (RASA1) tau, and p-tau (Ser396) proteins were determined by Western blot.ResultsThe results of Morris water maze showed that in the navigation experiment (from first day to the fifth day), the average escape latency of the rats exposed to three doses of aluminum was longer than that of the control rats (P

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.

Alzheimer’s disease (AD) is a representative neurodegenerative disease characterized by the structural and functional degeneration of neurons. The present study investigated the neuroprotective effect of Ixeris dentata (ID) extract on trimethyltin (TMT)-induced memory deficit in the rat. Cognitive improving effect and neuronal activity of ID were assessed by using Morris water maze (MWM) test and choline acetyltransferase (ChAT), cAMP-response element-binding protein (CREB) immunohistochemistry. Seven days after TMT injection (8.0 mg/kg, i.p.), each group of rats was administered saline, water extract of ID (WID, 400 or 800 mg/kg, p.o.), ethanol extract of ID (EID, 400 or 800 mg/kg, p.o.), or caffeic acid (CAF, 30 mg/kg, i.p.) daily for fourteen days. Results: Treatment with EID and CAF produced a significant improvement in escape latency time of the acquisition, and retention time in the target area of the MWM task. Additionally, administration of EID or CAF markedly alleviated TMT-induced loss of ChAT- and CREB-immunoreactive cells in the hippocampus. The results demonstrated that EID has a protective effect against TMT-induced memory deficit, partly through increasing the CREB and cholinergic signaling pathway in the hippocampus. These results suggest that ethanol extracts of ID might be useful for improving cognitive functions in neurodegenerative diseases such as Alzheimer’s disease.

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.

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]