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Cerebral ischemic stroke is a major cause of death worldwide due to brain cell death resulting from ischemia-reperfusion injury. However, effective treatment approaches for patients with ischemic stroke are still lacking in clinical practice. This study investigated the potential neuroprotective effects of sildenafil, a phosphodiesterase-5 inhibitor, in a gerbil model of global brain ischemia. We investigated the effects of sildenafil on the expression of glial fibrillary acidic protein and aquaporin-4, which are markers related to astrocyte activation and water homeostasis, respectively. Immunofluorescence analysis showed that the number of cells co-expressing these markers, which was elevated in the ischemia-induced group, was significantly reduced in the sildenafil-treated groups. This suggests that sildenafil may have a potential mitigating effect on astrocyte activation induced by ischemia. Additionally, we performed various behavioral tests, including the open-field test, novel object recognition, Barnes maze, Y-maze, and passive avoidance tests, to evaluate sildenafil's effect on cognitive function impaired by ischemia. Overall, the results suggest that sildenafil may serve as a neuroprotective agent, potentially alleviating delayed neuronal cell death and improving cognitive function impaired by ischemia. [ABSTRACT FROM AUTHOR]

Introduction: Suicide risk assessment based on self-report questionnaires is considered as problematic because risk states are dynamic and at-risk individuals may conceal suicidal intentions for several reasons. Therefore, recent research efforts increasingly focus on implicit risk markers such as the suicide attentional bias (SAB) measured with the Suicide Stroop Task (SST). However, most SST studies failed to demonstrate a SAB in individuals with suicide risk and repeatedly demonstrated insufficient psychometrics of the SST. This study aimed to investigate a SAB using a modified SST (M-SST) and to test its psychometric properties. Method: We compared n = 61 healthy controls and a high-risk inpatient sample of n = 40 suicide ideators and n = 40 suicide attempters regarding interference scores of positive, negative and suicide-related words. Interference scores were calculated by subtracting the mean reaction time (mean RT) of the neutral words from the mean RT of the suicide-related words (mean RT Suicide-mean RT Neutral), resulting in a suicide-specific interference score. Similarly, interference scores were calculated for the positive and negative words by subtracting the mean RT of neutral words from the mean RT of positive and negative words. Results: A Group x Interference ANOVA showed a significant interaction effect (p <.001, ηp2 = .09), indicating that group effects significantly vary across interference type. Post hoc comparisons revealed that both ideators and attempters demonstrated greater interferences only for suicide-related words compared to healthy controls, indicating a SAB in patients, while a difference between ideators and attempters was lacking. The suicide interference score classified with an AUC = 0.73, 95% CI [0.65 - 0.82], p <.001, between controls and patients with STBs. The M-SST demonstrated good internal consistency and convergent validity. Discussion: The study adds evidence to the assumptions of the Cognitive Model of Suicide, viewing a SAB as a cognitive marker of suicide vulnerability independently of the engagement in suicidal behavior. The results' clinical implications are discussed in the context of recommended intervention strategies during an acute suicidal state. Future studies with the M-SST should include non-suicidal patient controls to investigate whether a SAB is uniquely related to suicidality. [ABSTRACT FROM AUTHOR]

The aim of this study was to establish a multi-factor-induced depression model in mice within a relatively short period, specifically through the combination of intraperitoneal injection of lipopolysaccharide (LPS) and chronic restraint stress (CRS), and to evaluate the differences in depressive-like behaviors among three different strains of mice, seeking mouse strains more suitable for this combined model. The mice of each strain were randomly divided into the normal group and model group. The mice in the model group received a single intraperitoneal injection of LPS once daily (1 mg/kg/d for 7 days) and subsequent CRS for 6 h, to induce depression, while the mice in the normal group received no treatment. Behavioral tests: sucrose preference test (SPT), open field test (OFT), forced swim test (FST), and tail suspension test (TST) were conducted to assess depressive-like behaviors in the mice. Data analysis showed that there were significant intergroup differences in depressive-like behaviors in ICR and C57BL/6 J mice, while KM mice exhibited minor differences with relatively high deviation in individual behavioral score. This study indicated that the combined depression mouse model could successfully induce significant depressive-like behaviors in ICR and C57BL/6 J mice. [ABSTRACT FROM AUTHOR]

While the spatial distribution pattern of fish is increasingly used for toxicological test of chemicals or wastewater, no ideal parameter is available for quantitative assessment of spatial distribution, especially uneven distribution with multiple hotspots. Here, to develop a quantitative assessment parameter for spatial distribution, the zebrafish were exposed to ethanol, pentylenetetrazole (PTZ), paraquat dichloride (paraquat) and wastewater, followed by a behavioral test in a narrow tank. Behavioral data was acquired and analyzed by idTracker and MATLAB. By comparing the effects of all treatments on behavior parameters, we confirmed that the spatial distribution was more easily altered rather than general locomotor parameters, e.g. 0.7–70 mg/L PTZ and 5–20 mg/L paraquat being effective for altering spatial distribution but having little effects on general locomotor parameters. Based on the heatmap, i.e., the cumulative proportion of grids and that of frequency in grids, we calculated the behavioral Gini coefficient (G b) for quantitative assessment of fish spatial distribution. The Gini coefficient ranged from zero to 1, with larger values meaning poorer evenness of spatial distribution. Of note, G b showed smaller coefficient of variations (CV) with 3%-19% between replicate tanks in all treatments than the highest frequency (4%-79%), displaying well robustness. Especially, G b addressed the challenge of the complicated heatmap with multiple hotspots. Overall, the behavioral Gini coefficient we established is an ideal parameter to quantitatively assess spatial distribution of fish shoal, which is expected to be applied in toxicity testing for chemicals and wastewater and automatic quality monitoring for surface water and aquaculture water. [Display omitted] [ABSTRACT FROM AUTHOR]

Brucellosis is an infection widely distributed around the world, and in some countries it is considered a public health problem. Brucellosis causes insidious symptoms that make it difficult to diagnose. Infection can also trigger chronic pain and neuropsychiatric complications. Antibiotics are not always effective to eradicate infection, contributing to chronicity. We aimed to investigate the effects of antibiotic treatment on proinflammatory cytokines, neurotransmitters, corticosterone, and behavior in a murine model of infecrion of B. abortus strain 2308. Four study groups were created: (a) control; (b) antibiotic control; (c) infected with B. abortus 2308; and (d) infected and treated with rifampicin and doxycycline. We determined B. abortus 2308 colony-forming units (CFUs), the count of dendritic cells, and macrophages in the spleen; serum levels of cytokines and corticosterone; levels of serotonin, dopamine, epinephrine, and norepinephrine in the brain; and equilibrium, physical strength, anxiety, and hopelessness tests. The infected and treated mice group was compared with the control and infected mice to assess whether treatment is sufficient to recover neuroimmunoendocrine parameters. Our results showed that despite the treatment of brucellosis with rifampicin and doxycycline, antibiotic-treated mice showed a persistence of B. abortus 2308 CFUs, an increased count in macrophage number, and higher circulating levels of corticosterone. Furthermore, the levels of IL-12, IL-6, and TNF-α remained higher. We found a decrease in muscular strength and equilibrium concomitant to changes in neurotransmitters in the hippocampus, cerebellum, and frontal cortex. Our data suggest that the remaining bacterial load after antibiotic administration favors inflammatory, neurochemical, and behavioral alterations, partly explaining the widespread and paradoxical symptomatology experienced by patients with chronic brucellosis. [ABSTRACT FROM AUTHOR]

IntroductionSuicide risk assessment based on self-report questionnaires is considered as problematic because risk states are dynamic and at-risk individuals may conceal suicidal intentions for several reasons. Therefore, recent research efforts increasingly focus on implicit risk markers such as the suicide attentional bias (SAB) measured with the Suicide Stroop Task (SST). However, most SST studies failed to demonstrate a SAB in individuals with suicide risk and repeatedly demonstrated insufficient psychometrics of the SST. This study aimed to investigate a SAB using a modified SST (M-SST) and to test its psychometric properties.MethodWe compared n = 61 healthy controls and a high-risk inpatient sample of n = 40 suicide ideators and n = 40 suicide attempters regarding interference scores of positive, negative and suicide-related words. Interference scores were calculated by subtracting the mean reaction time (mean RT) of the neutral words from the mean RT of the suicide-related words (mean RT Suicide –mean RT Neutral), resulting in a suicide-specific interference score. Similarly, interference scores were calculated for the positive and negative words by subtracting the mean RT of neutral words from the mean RT of positive and negative words.ResultsA Group × Interference ANOVA showed a significant interaction effect (p

Hyperoxia is one of the key players contributing preterm brain injury. Researchers typically use rodent models to pinpoint the underlying pathologic alterations in hyperoxic brain damage. When evaluating the neurological effects of neonatal hyperoxic brain injury in an experimental model, choosing the appropriate assessment techniques is crucial. The goal of this article is to review the behavioral and learning tests that can be used to determine the impact of hyperoxia on the developing brain. Injuries to the nervous system can be recovered very quickly in newborn rodents. Thus, the timing of evaluation tests are very critical. A model that is appropriate for the brain's developmental processes and accurately simulates the damage in humans should be utilized in studies on neonatal hyperoxic brain injury, and the right test should be chosen at the appropriate time. In the first twenty days, physical and motor development tests, and subsequent evaluation of damaged brain structures are relevant. The open field and forced swim tests can be used to assess the animal's locomotor activity and depressive condition, while the watermaze, passive avoidance and new object recognition tests can be used to assess cognitive abilities. In laboratory mice and rats, physical development and motor reflex development tests can be started right after birth, while learning and memory tests can be done from 4 weeks at the earliest. Correlations between motor development, behavior, memory tests, and results of cellular/ molecular studies should be made and interpreted carefully.

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Background: Research reproducibility is a common problem in preclinical behavioral science. Mice are an important animal model for studying human behavioral disorders. Experimenters, processing methods, and rearing environments are the main causes of data variability in behavioral neuroscience. It is likely that mice adapt their behavior according to the environment outside the breeding cage. We speculated that mice housed on elevated shelves and mice housed on low shelves might have differently altered anxiety‐like behavior toward heights. Purpose: The purpose of this study was to investigate potential behavioral changes in mice raised at different heights for 3 weeks. Changes in behavior were examined using various experimental tests. Results: Mice housed on elevated shelves showed reduced anxiety‐like behavior in a light/dark traffic test compared with mice housed on low shelves. There were no significant differences between the two groups in terms of activity, exploratory behavior, muscle strength, or depression‐like behavior. Conclusions: Our results indicate that different cage heights and corresponding light exposure may alter the anxiety‐like behavior of mice in response to brightness. Researchers need to carefully control the cage height and light intensity experienced by the mice to produce reproducible test results. [ABSTRACT FROM AUTHOR]

Simple Summary: While several studies have focused on dogs' behavioral and emotional responses to sound stimuli, very few have addressed basic features of hearing, such as sensitivity. The latter is commonly described using the minimal intensities a subject can perceive at different frequencies, called hearing thresholds. To the best of our knowledge, only one behavioral study has explored this parameter in dogs. To strengthen the current knowledge on dogs' hearing abilities, we devised a behavioral testing procedure based on a staircase method, whereby the sound intensity assessed in one presentation is increased (i.e., made easier) if the dog failed in the previous presentation or decreased (made harder) if the dog succeeded in the previous presentation. In this way, dogs' sensitivity is evaluated through multiple assessments around the actual threshold, which increases the reliability of the result. We used this method to determine hearing thresholds at three frequencies (0.5, 4.0, and 20.0 kHz), testing five dogs per frequency. The hearing thresholds were found to be 19.5 ± 2.8 dB SPL at 0.5 kHz, 14.5 ± 4.5 dB SPL at 4.0 kHz, and 8.5 ± 12.8 dB SPL at 20.0 kHz. No improvement in performance was visible across the procedure. The results show that the staircase method is a feasible and reliable approach for assessing hearing thresholds in dogs. They also suggest that dogs might be more sensitive to high-frequency sounds than previously thought. This could be the result of selective pressure linked to intraspecific communication needs and potentially aid in low-range communication. There is a growing interest in performing playback experiments to understand which acoustical cues trigger specific behavioral/emotional responses in dogs. However, very limited studies have focused their attention on more basic aspects of hearing such as sensitivity, i.e., the identification of minimal intensity thresholds across different frequencies. Most previous studies relied on electrophysiological methods for audiograms for dogs, but these methods are considered less accurate than assessments based on behavioral responses. To our knowledge, only one study has established hearing thresholds using a behavioral assessment on four dogs but using a method that did not allow potential improvement throughout the sessions. In the present study, we devised an assessment procedure based on a staircase method. Implying the adaptation of the assessed intensity on the dogs' performance, this approach grants several assessments around the actual hearing threshold of the animal, thereby increasing the reliability of the result. We used such a method to determine hearing thresholds at three frequencies (0.5, 4.0, and 20.0 kHz). Five dogs were tested in each frequency. The hearing thresholds were found to be 19.5 ± 2.8 dB SPL at 0.5 kHz, 14.0 ± 4.5 dB SPL at 4.0 kHz, and 8.5 ± 12.8 dB SPL at 20.0 kHz. No improvement in performance was visible across the procedure. While the thresholds at 0.5 and 4.0 kHz were in line with the previous literature, the threshold at 20 kHz was remarkably lower than expected. Dogs' ability to produce vocalization beyond 20 kHz, potentially used in short-range communication, and the selective pressure linked to intraspecific communication in social canids are discussed as potential explanations for the sensitivity to higher frequencies. [ABSTRACT FROM AUTHOR]

Cerebral ischemic stroke is a major cause of death worldwide due to brain cell death resulting from ischemia-reperfusion injury. However, effective treatment approaches for patients with ischemic stroke are still lacking in clinical practice. This study investigated the potential neuroprotective effects of sildenafil, a phosphodiesterase-5 inhibitor, in a gerbil model of global brain ischemia. We investigated the effects of sildenafil on the expression of glial fibrillary acidic protein and aquaporin-4, which are markers related to astrocyte activation and water homeostasis, respectively. Immunofluorescence analysis showed that the number of cells co-expressing these markers, which was elevated in the ischemia-induced group, was significantly reduced in the sildenafil-treated groups. This suggests that sildenafil may have a potential mitigating effect on astrocyte activation induced by ischemia. Additionally, we performed various behavioral tests, including the open-field test, novel object recognition, Barnes maze, Y-maze, and passive avoidance tests, to evaluate sildenafil’s effect on cognitive function impaired by ischemia. Overall, the results suggest that sildenafil may serve as a neuroprotective agent, potentially alleviating delayed neuronal cell death and improving cognitive function impaired by ischemia.

Simple Summary: The poultry industry recognizes that handling day-old chicks in commercial hatcheries can lead to long-lasting changes in their behavior. However, these hatchery-related stresses are more intense and complex than those measured by traditional behavioral tests. This study developed a new behavioral handling test for day-old chickens by incorporating concepts from behavioral tests used with both young and adult birds. In the new test, 96 two-day-old chicks from seven breeds of native Japanese and Western chickens were used to evaluate 10 behavioral traits, including vocalization frequency and responses to human interaction. The results classified chicken temperaments into three categories: bustle, aggression, and timidity. These categories were used to classify the seven breeds. This new handling test provides a valuable tool for understanding the behavior of various chicken breeds and offers insights into their complex behaviors. It is well known in the poultry industry that fear and stress experienced during the handling of day-old chicks in commercial hatcheries can have long-lasting effects on their behavior later in life. These hatchery-related stresses are more intense and complex than those encountered in traditional behavioral tests. Consequently, a single behavioral test may not be sufficient to measure hatchery stresses and chicken temperament. In this study, we developed a new behavioral handling test for day-old chickens, which incorporated concepts from established behavioral tests used with both young and adult birds. The new test assessed 10 behavioral traits, including vocalization frequency and responses to human interaction. It was conducted on 96 two-day-old chicks from seven breeds of native Japanese and Western chickens. The results of the principal component analysis classified chicken temperaments into three distinct categories: bustle, aggression, and timidity. Using these categories, the seven breeds were classified into five groups, each with distinct temperaments. This study highlights the reliability and value of the new handling test in characterizing the temperaments of various chicken breeds and provides insights into the complex behaviors of chickens. [ABSTRACT FROM AUTHOR]

Abstract Background Research reproducibility is a common problem in preclinical behavioral science. Mice are an important animal model for studying human behavioral disorders. Experimenters, processing methods, and rearing environments are the main causes of data variability in behavioral neuroscience. It is likely that mice adapt their behavior according to the environment outside the breeding cage. We speculated that mice housed on elevated shelves and mice housed on low shelves might have differently altered anxiety‐like behavior toward heights. Purpose The purpose of this study was to investigate potential behavioral changes in mice raised at different heights for 3 weeks. Changes in behavior were examined using various experimental tests. Results Mice housed on elevated shelves showed reduced anxiety‐like behavior in a light/dark traffic test compared with mice housed on low shelves. There were no significant differences between the two groups in terms of activity, exploratory behavior, muscle strength, or depression‐like behavior. Conclusions Our results indicate that different cage heights and corresponding light exposure may alter the anxiety‐like behavior of mice in response to brightness. Researchers need to carefully control the cage height and light intensity experienced by the mice to produce reproducible test results.

Amyotrophic lateral sclerosis (ALS) is an extremely complex neurodegenerative disease involving different cell types, but motoneuronal loss represents its main pathological feature. Moreover, compensatory plastic changes taking place in parallel to neurodegeneration are likely to affect the timing of ALS onset and progression and, interestingly, they might represent a promising target for disease-modifying treatments. Therefore, a simplified animal model mimicking motoneuronal loss without the other pathological aspects of ALS has been established by means of intramuscular injection of cholera toxin-B saporin (CTB-Sap), which is a targeted neurotoxin able to kill motoneurons by retrograde suicide transport. Previous studies employing the mouse CTB-Sap model have proven that spontaneous motor recovery is possible after a subtotal removal of a spinal motoneuronal pool. Although these kinds of plastic changes are not enough to counteract the functional effects of the progressive motoneuron degeneration, it would nevertheless represent a promising target for treatments aiming to postpone ALS onset and/or delay disease progression. Herein, the mouse CTB-Sap model has been used to test the efficacy of mitochondrial division inhibitor 1 (Mdivi-1) as a tool to counteract the CTB-Sap toxicity and/or to promote neuroplasticity. The homeostasis of mitochondrial fission/fusion dynamics is indeed important for cell integrity, and it could be affected during neurodegeneration. Lesioned mice were treated with Mdivi-1 and then examined by a series of behavioral test and histological analyses. The results have shown that the drug may be capable of reducing functional deficits after the lesion and promoting synaptic plasticity and neuroprotection, thus representing a putative translational approach for motoneuron disorders.

Brucellosis is an infection widely distributed around the world, and in some countries it is considered a public health problem. Brucellosis causes insidious symptoms that make it difficult to diagnose. Infection can also trigger chronic pain and neuropsychiatric complications. Antibiotics are not always effective to eradicate infection, contributing to chronicity. We aimed to investigate the effects of antibiotic treatment on proinflammatory cytokines, neurotransmitters, corticosterone, and behavior in a murine model of infecrion of B. abortus strain 2308. Four study groups were created: (a) control; (b) antibiotic control; (c) infected with B. abortus 2308; and (d) infected and treated with rifampicin and doxycycline. We determined B. abortus 2308 colony-forming units (CFUs), the count of dendritic cells, and macrophages in the spleen; serum levels of cytokines and corticosterone; levels of serotonin, dopamine, epinephrine, and norepinephrine in the brain; and equilibrium, physical strength, anxiety, and hopelessness tests. The infected and treated mice group was compared with the control and infected mice to assess whether treatment is sufficient to recover neuroimmunoendocrine parameters. Our results showed that despite the treatment of brucellosis with rifampicin and doxycycline, antibiotic-treated mice showed a persistence of B. abortus 2308 CFUs, an increased count in macrophage number, and higher circulating levels of corticosterone. Furthermore, the levels of IL-12, IL-6, and TNF-α remained higher. We found a decrease in muscular strength and equilibrium concomitant to changes in neurotransmitters in the hippocampus, cerebellum, and frontal cortex. Our data suggest that the remaining bacterial load after antibiotic administration favors inflammatory, neurochemical, and behavioral alterations, partly explaining the widespread and paradoxical symptomatology experienced by patients with chronic brucellosis.

Apolipoprotein E (ApoE) is associated with Alzheimer’s disease (AD) and cognitive dysfunction in elderly individuals. There have been extensive studies on behavioral abnormalities in ApoE-deficient (Apoeshl) mice, which have been described as AD mouse models. Spontaneously hyperlipidemic mice were discovered in 1999 as ApoE-deficient mice due to ApoE gene mutations. However, behavioral abnormalities in commercially available Apoeshl mice remain unclear. Accordingly, we aimed to investigate the behavioral abnormalities of Apoeshl mice.

Neonicotinoid pesticides (NNs) transfer rapidly from mother to offspring, which exhibit neurobehavioral effects. However, no studies have investigated NNs' transgenerational effects. We exposed F0 generation mice (mothers) to a no-observed-adverse-effect level (NOAEL) of clothianidin (CLO) during gestation and lactation, and examined the adult neurobehavioral effects of three generations of offspring (F1, F2, F3). F1 had lower birth weight, decreased locomotor activity, and increased anxiety-like behavior. In F2, body weight was affected, and there was a decreasing trend in locomotor activity and an increasing trend in anxiety-like behavior. In F3, locomotor activity tended to increase. Thus, even when only the mothers were exposed, the effects of CLOs were still observed in F1, F2, and F3 but the effects became smaller. [ABSTRACT FROM AUTHOR]

Introduction: Post-traumatic stress disorder (PTSD) is a chronic mental illness triggered by traumatic experiences such as wars, natural disasters, or catastrophes, and it is characterized by anxiety, depression and cognitive impairment. Diosgenin is a steroidal sapogenin with known neuroprotective and antioxidant properties. This study aimed to assess the pharmacological potential of diosgenin in a single prolonged stress (SPS) model of PTSD, plus other behavioral models along with any consequent alterations in brain neurochemistry in male mice. Methodology: SPS was induced by restraining animals for 2 h, followed by 20 min of forced swim, recuperation for 15 min, and finally, exposure to ether to induce anesthesia. The SPS-exposed animals were treated with diosgenin (20, 40, and 60 mg/kg) and compared with the positive controls, fluoxetine or donepezil, then they were observed for any changes in anxiety/depression-like behaviors, and cognitive impairment. After behavioral screening, postmortem serotonin, noradrenaline, dopamine, vitamin C, adenosine and its metabolites inosine and hypoxanthine were quantified in the frontal cortex, hippocampus, and striatum by high-performance liquid chromatography. Additionally, animal serum was screened for changes in corticosterone levels. Results: The results showed that diosgenin reversed anxiety- and depression-like behaviors, and ameliorated cognitive impairment in a dose-dependent manner. Additionally, diosgenin restored monoamine and vitamin C levels dose-dependently and modulated adenosine and its metabolites in the brain regions. Diosgenin also reinstated otherwise increased serum corticosterone levels in SPS mice. Conclusion: The findings suggest that diosgenin may be a potential candidate for improving symptoms of PTSD. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), one of the most prevalent neurodegenerative diseases is associated with pathological autophagy-lysosomal pathway dysfunction. Dexmedetomidine (Dex) has been suggested as an adjuvant to general anesthesia with advantages in reducing the incidence of postoperative cognitive dysfunction in Dex-treated patients with AD and older individuals. Several studies reported that Dex improved memory; however, evidence on the effects of Dex on neuronal autophagy dysfunction in the AD model is lacking. We hypothesized that Dex administration would have neuroprotective effects by improving pathological autophagy dysfunction in mice that received an intracerebroventricular (i.c.v.) injection of amyloid β-protein fragment 25-35 (Aβ25--35) and in an autophagy-deficient cellular model. In the Y-maze test, Dex reversed the decreased activity of Aβ25--35 mice. Additionally, it restored the levels of two memory-related proteins, phosphorylated Ca2+/calmodulin-dependent protein kinase II (p-CaMKII) and postsynaptic density-95 (PSD-95) in Aβ25-35 mice and organotypic hippocampal slice culture (OHSC) with Aβ25-35. Dex administration also resulted in decreased expression of the autophagy-related microtubule-associated proteins light chain 3-II (LC3-II), p62, lysosome-associated membrane protein2 (LAMP2), and cathepsin D in Aβ25-35 mice and OHSC with Aβ25-35. Increased numbers of co-localized puncta of LC3-LAMP2 or LC3-cathepsin D, along with dissociated LC3-p62 immunoreactivity following Dex treatment, were observed. These findings were consistent with the results of western blots and the transformation of double-membrane autophagosomes into single-membraned autolysosomes in ultrastructures. It was evident that Dex treatment alleviated impaired autolysosome formation in Aβ mice. Our study demonstrated the improvement of memory impairment caused by Dex and its neuroprotective mechanism by investigating the role of the autophagy-lysosomal pathway in a murine Aβ25-35 model. These findings suggest that Dex could be used as a potential neuroprotective adjuvant in general anesthesia to prevent cognitive decline. [ABSTRACT FROM AUTHOR]

Activation of the interleukin-4 (IL-4) pathway ameliorates secondary injury mechanisms after experimental traumatic brain injury (TBI); therefore, we assessed the effect of a therapeutic IL-4 administration on secondary brain damage after experimental TBI. We subjected 100 C57/Bl6 wildtype mice to controlled cortical impact (CCI) and administered IL-4 or a placebo control subcutaneously 15 min thereafter. Contusion volume (Nissl staining), neurological function (hole board, video open field, and CatWalkXT®), and the immune response (immunofluorescent staining) were analyzed up to 28 days post injury (dpi). Contusion volumes were significantly reduced after IL-4 treatment up to 14 dpi (e.g., 6.47 ± 0.41 mm3 vs. 3.80 ± 0.85 mm3, p = 0.011 3 dpi). Macrophage invasion and microglial response were significantly attenuated in the IL-4 group in the acute phase after CCI (e.g., 1.79 ± 0.15 Iba-1+/CD86+ cells/sROI vs. 1.06 ± 0.21 Iba-1/CD86+ cells/sROI, p = 0.030 in the penumbra 3 dpi), whereas we observed an increased neuroinflammation thereafter (e.g., mean GFAP intensity of 3296.04 ± 354.21 U vs. 6408.65 ± 999.54 U, p = 0.026 in the ipsilateral hippocampus 7 dpi). In terms of functional outcome, several gait parameters were improved in the acute phase following IL-4 treatment (e.g., a difference in max intensity of −7.58 ± 2.00 U vs. −2.71 ± 2.44 U, p = 0.041 3 dpi). In conclusion, the early single-dose administration of IL-4 significantly reduces secondary brain damage in the acute phase after experimental TBI in mice, which seems to be mediated by attenuation of macrophage and microglial invasion. [ABSTRACT FROM AUTHOR]

Purpose: Although escitalopram is known to be an effective drug for adult depression, its disease-modifying efficacy on adolescents remains controversial. The present study aimed to evaluate the therapeutic effect of escitalopram on behavioral aspects as well as functional neural circuits by means of positron emission tomography. Procedures: To generate the animal models of depression, restraint stress was used during the peri-adolescent period (RS group). Thereafter, escitalopram was administered after the end of stress exposure (Tx group). We performed NeuroPET studies of glutamate, glutamate, GABA, and serotonin systems. Results: The Tx group showed no body weight change compared to the RS group. In the behavioral tests, the Tx group also displayed the similar time spent in open arms and immobility time to those for RS. In the PET studies, brain uptake values for the Tx group revealed no significant differences in terms of glucose, GABAA, and 5-HT1A receptor densities, but lower mGluR5 PET uptake compared to the RS group. In the immunohistochemistry, the Tx group showed the significant loss of neuronal cells in the hippocampus compared to the RS group. Conclusion: The administration of escitalopram had no therapeutic effect on the adolescent depression. [ABSTRACT FROM AUTHOR]

Simple Summary: The disruption of circadian rhythms is considered a potential source of distress, but the extent of its consequences is under study. This research investigated whether the disruption of the light/dark and feeding/fasting cycles can trigger stress and anxiety-like behavior in fish. For this purpose, we first optimized behavioral tests to measure anxiety-like states in goldfish. Second, we studied anxiety and stress responses in two groups of goldfish exposed to either continuous light or randomly scheduled meals for two months. Both conditions led to anxiety-like behavior, evidenced by increased thigmotaxis in the open field with object approach task. Fish exposed to constant light also showed higher locomotor activity, suggesting greater energy expenditure. Additionally, chronodisruption led to increased cortisol levels throughout the experiment, with evidence of a possible axis fatigue due to chronic stress in fish under continuous light. Altogether, these findings support that these chronodisruptive conditions cause distress in the animals, and they should be considered for welfare improvement. The correlation analyses suggested that cortisol, thigmotaxis, and scototaxis are not dependent on each other, while there is a high influence of individual behavioral traits. Thus, the need for combining multiple parameters when assessing discomfort in fish is emphasized. Chronodisruption caused by factors such as light at night and mistimed meals has been linked to numerous physiological alterations in vertebrates and may be an anxiogenic factor affecting welfare. This study aims to investigate whether chronodisruption causes measurable changes in the anxiety responses of goldfish under two conditions: randomly scheduled feeding (RF) and continuous light (LL). Anxiety-like behavior was assessed in the open field with object approach and black/white preference tests, which had been validated using diazepam. An increased thigmotaxis response and decreased object exploration under both chronodisruption protocols indicated anxiety states. Furthermore, locomotor activity was increased in LL fish. The black/white preference test discriminated anxiolysis induced by diazepam but was unable to detect anxiety caused by chronodisruption. Plasma cortisol increased in both RF and LL fish throughout the experiment, confirming that both conditions caused stress. The LL fish also showed an apparently desensitized hypothalamus–pituitary–interrenal HPI axis, with a decrease in pomc and crf expression. Individual analysis found no correlation between anxiety-like behavior and stress axis activation nor between scototaxis and thigmotaxis responses. However, individual differences in sensitivity to each test were detected. Altogether, these results highlight circadian disruption as a stressor for fish and endorse a multiple variable approach for reliably assessing animal discomfort. [ABSTRACT FROM AUTHOR]

There is a growing interest in performing playback experiments to understand which acoustical cues trigger specific behavioral/emotional responses in dogs. However, very limited studies have focused their attention on more basic aspects of hearing such as sensitivity, i.e., the identification of minimal intensity thresholds across different frequencies. Most previous studies relied on electrophysiological methods for audiograms for dogs, but these methods are considered less accurate than assessments based on behavioral responses. To our knowledge, only one study has established hearing thresholds using a behavioral assessment on four dogs but using a method that did not allow potential improvement throughout the sessions. In the present study, we devised an assessment procedure based on a staircase method. Implying the adaptation of the assessed intensity on the dogs’ performance, this approach grants several assessments around the actual hearing threshold of the animal, thereby increasing the reliability of the result. We used such a method to determine hearing thresholds at three frequencies (0.5, 4.0, and 20.0 kHz). Five dogs were tested in each frequency. The hearing thresholds were found to be 19.5 ± 2.8 dB SPL at 0.5 kHz, 14.0 ± 4.5 dB SPL at 4.0 kHz, and 8.5 ± 12.8 dB SPL at 20.0 kHz. No improvement in performance was visible across the procedure. While the thresholds at 0.5 and 4.0 kHz were in line with the previous literature, the threshold at 20 kHz was remarkably lower than expected. Dogs’ ability to produce vocalization beyond 20 kHz, potentially used in short-range communication, and the selective pressure linked to intraspecific communication in social canids are discussed as potential explanations for the sensitivity to higher frequencies.

Scopolamine is a well-known pharmacological agent responsible for causing memory impairment in animals, as well as oxidative stress and neuroinflammation inducer which lead to the development of Alzheimer disease. Although a cure for Alzheimer’s disease is unavailable. Ranuncoside, a metabolite obtained from a medicinal plant has demonstrated antioxidant and anti-inflammatory properties in vitro, making it a promising treatment with potential anti-Alzheimer disease properties. However, as ranuncoside has not been evaluated for its antioxidant and anti-neuroinflammatory properties in any in vivo model, our study aimed to evaluate its neurotherapeutic efficacy against scopolamine-induced memory impairment in adult male albino mice.Mice were randomly divided into four experimental groups. Mice of group I was injected with saline, group II was injected with scopolamine (1 mg/kg/day) for 3 weeks. After receiving a daily injection of scopolamine for 1 week, the mice of group III were injected with ranuncoside (10 mg/kg) every other day for 2 weeks along with scopolamine daily and group IV were injected with ranuncoside on 5th alternate days. Behavioral tests (i.e., Morris water maze and Y-maze) were performed to determine the memory-enhancing effect of ranuncoside against scopolamine's memory deleterious effect. Western blot analysis was also performed to further elucidate the anti-neuroinflammatory and antioxidant effects of ranuncoside against scopolamine-induced neuroinflammation and oxidative stress.Our results showed memory-enhancing, anti-neuroinflammatory effect, and antioxidant effects of ranuncoside against scopolamine by increasing the expression of the endogenous antioxidant system (i.e., Nrf2 and HO-1), followed by blocking neuroinflammatory markers such as NF-κB, COX-2, and TNF-α. The results also revealed that ranuncoside possesses hypoglycemic and hypolipidemic effects against scopolamine-induced hyperglycemia and hyperlipidemia in mice as well as scopolamine’s hyperglycemic effect. In conclusion, our findings suggest that ranuncoside could be a potential agent for the management of Alzheimer’s disease, hyperglycemia, and hyperlipidemia.

Introduction: Post-traumatic stress disorder (PTSD) is a chronic mental illness triggered by traumatic experiences such as wars, natural disasters, or catastrophes, and it is characterized by anxiety, depression and cognitive impairment. Diosgenin is a steroidal sapogenin with known neuroprotective and antioxidant properties. This study aimed to assess the pharmacological potential of diosgenin in a single prolonged stress (SPS) model of PTSD, plus other behavioral models along with any consequent alterations in brain neurochemistry in male mice.Methodology: SPS was induced by restraining animals for 2 h, followed by 20 min of forced swim, recuperation for 15 min, and finally, exposure to ether to induce anesthesia. The SPS-exposed animals were treated with diosgenin (20, 40, and 60 mg/kg) and compared with the positive controls, fluoxetine or donepezil, then they were observed for any changes in anxiety/depression-like behaviors, and cognitive impairment. After behavioral screening, postmortem serotonin, noradrenaline, dopamine, vitamin C, adenosine and its metabolites inosine and hypoxanthine were quantified in the frontal cortex, hippocampus, and striatum by high-performance liquid chromatography. Additionally, animal serum was screened for changes in corticosterone levels.Results: The results showed that diosgenin reversed anxiety- and depression-like behaviors, and ameliorated cognitive impairment in a dose-dependent manner. Additionally, diosgenin restored monoamine and vitamin C levels dose-dependently and modulated adenosine and its metabolites in the brain regions. Diosgenin also reinstated otherwise increased serum corticosterone levels in SPS mice.Conclusion: The findings suggest that diosgenin may be a potential candidate for improving symptoms of PTSD.

Alzheimer’s disease (AD), one of the most prevalent neurodegenerative diseases is associated with pathological autophagy-lysosomal pathway dysfunction. Dexmedetomidine (Dex) has been suggested as an adjuvant to general anesthesia with advantages in reducing the incidence of postoperative cognitive dysfunction in Dex-treated patients with AD and older individuals. Several studies reported that Dex improved memory; however, evidence on the effects of Dex on neuronal autophagy dysfunction in the AD model is lacking. We hypothesized that Dex administration would have neuroprotective effects by improving pathological autophagy dysfunction in mice that received an intracerebroventricular (i.c.v.) injection of amyloid β-protein fragment 25–35 (Aβ25–35) and in an autophagy-deficient cellular model. In the Y-maze test, Dex reversed the decreased activity of Aβ25–35 mice. Additionally, it restored the levels of two memory-related proteins, phosphorylated Ca2+/calmodulin-dependent protein kinase II (p-CaMKII) and postsynaptic density-95 (PSD-95) in Aβ25–35 mice and organotypic hippocampal slice culture (OHSC) with Aβ25–35. Dex administration also resulted in decreased expression of the autophagy-related microtubule-associated proteins light chain 3-II (LC3-II), p62, lysosome-associated membrane protein2 (LAMP2), and cathepsin D in Aβ25–35 mice and OHSC with Aβ25–35. Increased numbers of co-localized puncta of LC3-LAMP2 or LC3-cathepsin D, along with dissociated LC3-p62 immunoreactivity following Dex treatment, were observed. These findings were consistent with the results of western blots and the transformation of double-membrane autophagosomes into single-membraned autolysosomes in ultrastructures. It was evident that Dex treatment alleviated impaired autolysosome formation in Aβ mice. Our study demonstrated the improvement of memory impairment caused by Dex and its neuroprotective mechanism by investigating the role of the autophagy-lysosomal pathway in a murine Aβ25–35 model. These findings suggest that Dex could be used as a potential neuroprotective adjuvant in general anesthesia to prevent cognitive decline.

Animal behavioral tests are often conducted during the day. However, rodents are nocturnal animals and are primarily active at night. The aim of this study was to determine whether there are diurnal changes in cognitive and anxiety‐like performance of mice following chronic sleep restriction (SR). We also investigated whether this phenotypic difference is related to the diurnal variation of glymphatic clearance of metabolic wastes. Mice received 9‐day SR by the use of the modified rotating rod method, followed by the open field, elevated plus maze, and Y‐maze tests conducted during the day and at night, respectively. Brain β‐amyloid (Aβ) and tau protein levels, the polarity of aquaporin4 (AQP4), a functional marker of the glymphatic system, and glymphatic transport ability were also analyzed. SR mice exhibited cognitive impairment and anxiety‐like behaviors during the day, but not at night. AQP4 polarity and glymphatic transport ability were higher during the day, with lower Aβ1‐42, Aβ1‐40, and P‐Tau levels in the frontal cortex. These day‐night differences were totally disrupted after SR. These results reveal the diurnal changes in behavioral performance after chronic SR, which may be related to circadian control of AQP4‐mediated glymphatic clearance of toxic macromolecules from the brain. [ABSTRACT FROM AUTHOR]

Neonicotinoid pesticides (NN) were recently reported to exhibit adverse effects in higher vertebrates. Moreover, NNs are routinely transferred from mother to offspring, raising concerns about their effects on future generations. The fetal and neonatal periods are the most critical to the formation of neural circuits in the brain through neurogenesis and differentiation, neuronal migration, axon guidance, and synaptogenesis. NN exposure throughout the fetal and neonatal periods was found to affect the neurobehavior of the offspring, but the stage-specific neurobehavioral effects are unclear. We exposed fetal and neonatal mice to a no-observed-adverseeffect level (NOAEL) of clothianidin (CLO) for 4 days during each of four developmental stages: neurite proliferation and differentiation (fetal days 9-12, CLO-1), neurite outgrowth (fetal days 15-18, CLO-2), synapse formation and astrocyte differentiation (days 1-4 after birth, CLO-3), and synapse remodeling (days 11-14 after birth, CLO-4). CLO's neurobehavioral effects were evaluated in juveniles and adults, revealing that CLO-1 and CLO-2 caused behavioral abnormalities in adult mice. CLO-3 significantly increased locomotor activity and decreased juvenile neurons in the hippocampal dentate gyrus in adulthood. Comprehensive gene analysis of CLO-3 revealed high expression of genes related to neurite outgrowth and axonal branching in the hippocampus in juveniles and adults. These results revealed developmental stage-specific effects of a NOAEL of CLO in the fetal and neonatal periods, suggesting that the susceptibility of the fetus and neonate to CLO varies by developmental stage. [ABSTRACT FROM AUTHOR]

Simple Summary: In humans and mice, the olfactory system is linked to areas of the brain that modulate behavior. Malfunctions of the olfactory system were described in many neurological and psychiatric diseases, including Alzheimer's and Parkinson's disease, depression, and mood disorders. Some of these diseases are common in aging persons; hence, it is relevant to know how the olfactory bulb, the first olfactory center in the brain, changes with age in its structure, and how these changes may be related to behavioral modifications. Since most of the experimental work is performed in mice, we studied young and elderly mice with a battery of behavioral tests to describe the differences in motor, olfactory, cognitive, and emotional performance. Then, mice underwent magnetic resonance imaging to describe the differences between olfactory bulbs of young and elderly mice. Lastly, we selected the behavioral variables more predictive of the differences between young and elderly mice and correlated them with the most predictive magnetic resonance variables. Elderly mice were less scared than young mice by new environments, and their olfactory bulb differed in two structural variables, which correlated with three anxiety measures. These data suggest a new direction for human aging studies, on the link between the olfactory bulb and behavior. Olfactory areas in mammalian brains are linked to centers that modulate behavior. During aging, sensitivity to odors decreases and structural changes are described in olfactory areas. We explored, in two groups of male mice (young and elderly, 6 and 19 months old, respectively), the link between the changes in olfactory bulb structure, detected with magnetic resonance imaging, and behavioral changes in a battery of tests on motor, olfactory, cognitive performance, and emotional reactivity. The behavioral pattern of elderly mice appears less anxious, being less scared by new situations. Additionally, the olfactory bulb of young and elderly mice differed in two variables derived from magnetic resonance imaging (fractional anisotropy and T2 maps). A random forest approach allowed to select the variables most predictive of the differences between young and elderly mice, and correlations were found between three behavioral variables indicative of anxious behavior and the two magnetic resonance variables mentioned above. These data suggest that in the living mouse, it is possible to describe co-occurring age-related behavioral and structural changes in the olfactory bulb. These data serve as a basis for studies on normal and pathological aging in the mouse, but also open new opportunities for in vivo human aging studies. [ABSTRACT FROM AUTHOR]

Background: Leucine‐rich repeat kinase 2 (LRRK2) mutation is a common genetic risk factor of Parkinson's disease (PD). Presynaptic dysfunction is an early pathogenic event associated with dopamine (DA) dysregulation in striatum of the brain. DA uptake activity of DA uptake transporter (DAT) affects synaptic plasticity and motor and non‐motor behavior. Synaptogyrin‐3 (SYNGR3) is part of the synaptogyrin family, especially abundant in brain. Previous in vitro studies demonstrated interaction between SYNGR3 and DAT. Reduced SYNGR3 expression was observed in human PD brains with unclear reasons. Methods: Here, we further explored whether inducing SYNGR3 expression can influence (i) cellular DA uptake using differentiated human SH‐SY5Y neuronal cells, (ii) striatal synaptosomal DA uptake in a mutant LRRK2R1441G knockin mouse model of PD, and (iii) innate rodent behavior using the marble burying test. Results: Young LRRK2 mutant mice exhibited significantly lower SYNGR3 levels in striatum compared to age‐matched wild‐type (WT) controls, resembling level in aged WT mice. SYNGR3 is spatially co‐localized with DAT at striatal presynaptic terminals, visualized by immuno‐gold transmission electron microscopy and immunohistochemistry. Their protein–protein interaction was confirmed by co‐immunoprecipitation. Transient overexpression of SYNGR3 in differentiated SH‐SY5Y cells increased cellular DA uptake activity without affecting total DAT levels. Inducing SYNGR3 overexpression by adeno‐associated virus‐7 (AAV7) injection in vivo into striatum increased ex vivo synaptosomal DA uptake in LRRK2 mutant mice and improved their innate marble burying behavior. Conclusion: Brain SYNGR3 expression may be an important determinant to striatal DA homeostasis and synaptic function. Our preliminary behavioral test showed improved innate behavior after SYNGR3 overexpression in LRRK2 mutant mice, advocating further studies to determine the influence of SYNGR3 in the pathophysiology of DA neurons in PD. [ABSTRACT FROM AUTHOR]

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IntroductionThe welfare of breeding boars is often overlooked, resulting in limited scientific data to foster discussion of the topic. We aimed to investigate the effect of different boar housing conditions on their offspring’s emotionality.MethodsEighteen boars were housed in three different conditions: crates (C; n = 6), pens (P; n = 6), or enriched pens (E; n = 6). Boars were distributed by semen quality (SQ; high, medium, or low). Three semen pools were used to inseminate 13 gilts housed in outdoor paddocks. At 25 days of age, 138 suckling piglets were subjected to open field (OF), novel object (NO), and elevated plus-maze (EPM) tests. Saliva was collected before and after the OF and NO tests to measure cortisol concentrations. At the end of the experiment, hair samples were collected for DNA paternity tests. Piglets were classified based on their behavioral responses using hierarchical cluster analysis of the principal components extracted from factor analysis of mixed data. The variables were reduced to seven principal components (dimensions, Dims), which explained 73% of the total variation, and were analyzed using linear mixed models. The models included each Dim as a dependent variable, paternal treatment and body weight (BW) as fixed effects, and paternal SQ as a random effect. Kruskal−Wallis and Wilcoxon rank-sum tests were used to compare the cortisol concentration ratios (before and after the OF and NO tests) between groups.ResultsThere was an effect of treatment on Dim 3 (EPM; activity/fear), with higher values in C piglets than E piglets (p = 0.047). Although C piglets had significantly higher values than P piglets in Dim 4 (EPM; anxiety; p = 0.029) and Dim 6 (NO; inactivity far from the object/exploration; p

It is well known in the poultry industry that fear and stress experienced during the handling of day-old chicks in commercial hatcheries can have long-lasting effects on their behavior later in life. These hatchery-related stresses are more intense and complex than those encountered in traditional behavioral tests. Consequently, a single behavioral test may not be sufficient to measure hatchery stresses and chicken temperament. In this study, we developed a new behavioral handling test for day-old chickens, which incorporated concepts from established behavioral tests used with both young and adult birds. The new test assessed 10 behavioral traits, including vocalization frequency and responses to human interaction. It was conducted on 96 two-day-old chicks from seven breeds of native Japanese and Western chickens. The results of the principal component analysis classified chicken temperaments into three distinct categories: bustle, aggression, and timidity. Using these categories, the seven breeds were classified into five groups, each with distinct temperaments. This study highlights the reliability and value of the new handling test in characterizing the temperaments of various chicken breeds and provides insights into the complex behaviors of chickens.

Abstract Background Leucine‐rich repeat kinase 2 (LRRK2) mutation is a common genetic risk factor of Parkinson's disease (PD). Presynaptic dysfunction is an early pathogenic event associated with dopamine (DA) dysregulation in striatum of the brain. DA uptake activity of DA uptake transporter (DAT) affects synaptic plasticity and motor and non‐motor behavior. Synaptogyrin‐3 (SYNGR3) is part of the synaptogyrin family, especially abundant in brain. Previous in vitro studies demonstrated interaction between SYNGR3 and DAT. Reduced SYNGR3 expression was observed in human PD brains with unclear reasons. Methods Here, we further explored whether inducing SYNGR3 expression can influence (i) cellular DA uptake using differentiated human SH‐SY5Y neuronal cells, (ii) striatal synaptosomal DA uptake in a mutant LRRK2R1441G knockin mouse model of PD, and (iii) innate rodent behavior using the marble burying test. Results Young LRRK2 mutant mice exhibited significantly lower SYNGR3 levels in striatum compared to age‐matched wild‐type (WT) controls, resembling level in aged WT mice. SYNGR3 is spatially co‐localized with DAT at striatal presynaptic terminals, visualized by immuno‐gold transmission electron microscopy and immunohistochemistry. Their protein–protein interaction was confirmed by co‐immunoprecipitation. Transient overexpression of SYNGR3 in differentiated SH‐SY5Y cells increased cellular DA uptake activity without affecting total DAT levels. Inducing SYNGR3 overexpression by adeno‐associated virus‐7 (AAV7) injection in vivo into striatum increased ex vivo synaptosomal DA uptake in LRRK2 mutant mice and improved their innate marble burying behavior. Conclusion Brain SYNGR3 expression may be an important determinant to striatal DA homeostasis and synaptic function. Our preliminary behavioral test showed improved innate behavior after SYNGR3 overexpression in LRRK2 mutant mice, advocating further studies to determine the influence of SYNGR3 in the pathophysiology of DA neurons in PD.

Introduction: Our aim is to reduce the side effects and increase the efficiency of donepezil by formulating donepezil-loaded poly(lactic-coglycolic acid)-block-poly(ethylene glycol) nanoparticles (NPs) directly targeting amyloid beta (Aβ) fibrils in the brain and evaluate behavioral changes in this fibril model of AD. Methods: AD model was developed by intracerebroventricular injection of pre-aggregated β25-35 fibrils. Rats were intravenously administered either solvent, donepezil-loaded NPs (15µg/kg) or free donepezil (1mg/ kg) 3 times for a week except for naïve controls. The effect of treatments on anxiety, motor functions, and cognitive functions was tested by elevated plus maze, locomotor activity, novel object recognition, and Morris's water maze tests, respectively. Results: Accumulation of Aβ25-35 fibrils in brain sections was confirmed. Anxiety-like behavior was observed in the Aβ Alzheimer and free donepezil treatment groups while donepezil-loaded NP treatment showed hypo-anxiety-like behavior. Donepezil-loaded NPs were successful in treatment of short-term memory deficit better than free donepezil injection. In Morris's water maze, both donepezil-loaded NPs and free donepezil groups found the platform in shorter time compared to Aβ Alzheimer group. In locomotor activity test, both donepezil treated groups moved less than the Aβ Alzheimer group and naïve controls. After the pharmacological experiments, acetylcholinesterase activity was determined and showed an increase in Aβ Alzheimer group compared to controls. Donepezil-loaded NPs inhibited the acetylcholinesterase activity more efficiently than the free donepezil group. Conclusion: Targeting with donepezil-loaded PLGA-b-PEG-NPs increases efficiency, helps to inhibit acetylcholinesterase activity more substantially, improves cognitive decline due to its longer duration of action and destabilizing effect on amyloid fibrils. [ABSTRACT FROM AUTHOR]

Background: D-ribose is an aldehyde sugar and a necessary component of all living cells. Numerous reports have focused on D-ribose intervention in animal models to assess the negative effects of D-ribose on cognition. However, the results across these studies are inconsistent and the doses and actual effects of D-ribose on cognition remain unclear. This systematic review aimed to evaluate the effect of D-ribose on cognition in rodents. Methods: The articles from PubMed, Embase, Sciverse Scopus, Web of Science, the Chinese National Knowledge Infrastructure, SinoMed, Wanfang, and Cqvip databases were screened. The results from the abstract on cognitive-related behavioral tests and biochemical markers from the included articles were extracted and the reporting quality was assessed. Results: A total of eight trials involving 289 rodents met the eligibility criteria, and both low- and high-dose groups were included. Meta-analyses of these studies showed that D-ribose could cause a significant decrease in the number of platform crossings (standardized mean difference [SMD]: -0.80; 95% CI: -1.14, -0.46; p < 0.00001), percentage of distance traversed in the target quadrant (SMD: -1.20; 95% CI: -1.47, -0.92; p < 0.00001), percentage of time spent in the target quadrant (SMD: -0.93; 95% CI: -1.18, -0.68; p < 0.00001), and prolonged escape latency (SMD: 0.41; 95% CI: 0.16, 0.65; p = 0.001) in the Morris water maze test. Moreover, D-ribose intervention increased the levels of advanced glycation end products (AGEs) in the brain (SMD: 0.49; 95% CI: 0.34, 0.63; p < 0.00001) and blood (SMD: 0.50; 95% CI: 0.08, 0.92; p = 0.02). Subsequently, subgroup analysis for the dose of Dribose intervention revealed that high doses injured cognitive function more significantly than low D-ribose doses. Conclusion: D-ribose treatment caused cognitive impairment, and cognition deteriorated with increasing dose. Furthermore, the increase in AGEs in the blood and brain confirmed that D-ribose may be involved in cognitive impairment through non-enzymatic glycosylation resulting in the generation of AGEs. These findings provide a new research idea for unveiling basic mechanisms and prospective therapeutic targets for the prevention and treatment of patients with cognitive impairment. [ABSTRACT FROM AUTHOR]

Abstract Background Angiostrongylus cantonensis is also known as rat lungworm. Infection with this parasite is a zoonosis that can cause eosinophilic meningitis and/or eosinophilic meningoencephalitis in humans and may lead to fatal outcomes in severe cases. In this study, we explored the mechanisms of the impairments in the cognitive functions of mice infected with A. cantonensis. Methods In infected mice with different infective intensities at different timepoint postinfection, loss and recovery of cognitive functions such as learning and memory abilities were determined. Neuronal death and damage to synaptic structures were analyzed by Western blotting and IHC in infected mice with different infection intensities at different timepoint postinfection. Results The results of behavioral tests, pathological examinations, and Golgi staining showed that nerve damage caused by infection in mice occurred earlier than pathological changes of the brain. BDNF was expressed on 14 day post-infection. Cleaved caspase-3 increased significantly in the late stage of infection. However, IHC on NeuN indicated that no significant changes in the number of neurons were found between the infected and uninfected groups. Conclusions The synaptic loss caused by the infection of A. cantonensis provides a possible explanation for the impairment of cognitive functions in mice. The loss of cognitive functions may occur before severe immunological and pathological changes in the infected host.

• This article is the first to study the antidepressant effect of Cimicifuga dahurica and its mechanism of action. • Cimicifuga dahurica has good neuroprotective effects on injured PC12 cells induced by corticosterone and drug-induced depression models. • Cimicifuga dahurica (60 mg/kg and 120 mg/kg) can significantly increase monoamine neurotransmitter levels in the hippocampus and frontal cortex of mice. • Cimicifuga dahurica can effectively produce an antidepressant-like effect via monoamine regulatory pathways. Sheng-ma is recorded in the Compendium of Materia Medica and mainly originates from the rhizomes of Cimicifuga dahurica (Turcz.) Maxim. (CD), Cimicifuga heracleifolia Kom. and Cimicifuga foetida L. The alcoholic extract of Cimicifuga foetida L. (Brand name: Ximingting®) has been approved for the treatment of perimenopausal symptoms accompanying hot flash, depression and anxiety in China. However, there's no further study about the antidepressant-like effects of C. dahurica (CD). The aim of this study is to investigate the antidepressant-like effect of CD extracted by 75% ethanol and its possible mechanisms.The neuro-protective effects of CD on injured PC12 cells induced by corticosterone was measured firstly. Then, forced swim test (FST), tail suspension test (TST), reserpine-induced hypothermia, 5-hydroxytryptophan (5-HTP) induced head twitch response in mice and chronic unpredictable mild stress (CUMS) on sucrose preference tests were executed. Moreover, the potential mechanisms were explored by measuring levels of monoamine neurotransmitter in mice frontal cortex and hippocampus, testing monoamine oxidase enzyme A (MAO-A) activities in the brains of CUMS-exposed mice. Results showed that CD (60, 120 mg/kg) can significantly decreased the immobility period in FST and TST in mice without affecting locomotor activity. CD (30 mg/kg, 60 mg/kg, 120 mg/kg) could significantly counteracted reserpine-induced hypothermia and increased the number of head-twitches in 5-HTP induced head twitch response. It was also found that the monoamine neurotransmitter levels in the hippocampus and frontal cortex were significantly increased in 60 mg/kg and 120 mg/kg CD treated mice. In addition, CD (60 and 120 mg/kg) significantly inhibited MAO-A after 6-week CUMS exposure. CD can effectively produce an antidepressant-like effect, which involved with modulation of monoamine regulatory pathways. [Display omitted] [ABSTRACT FROM AUTHOR]

The study introduced and evaluated learning paradigms for Maylandia callainos cichlids using a modified version of the rodent T-maze, filled with tank water (the "sunken" modification). Both male and female fish underwent training in two distinct conditioning paradigms. Firstly, simple operant conditioning involved placing a food reward in either the right or left compartment. Cichlids demonstrated the ability to purposefully find the bait within 6 days of training, with a persistent place preference lasting up to 6 days. Additionally, the learning dynamics varied with sex: female cichlids exhibited reduction in latency to visit the target compartment and consume the bait, along with a decrease in the number of errors 3 and 4 days earlier than males, respectively. Secondly, visually-cued operant conditioning was conducted, with a food reward exclusively placed in the yellow compartment, randomly positioned on the left or right side of the maze during each training session. Visual learning persisted for 10 days until reaction time improvement plateaued. Color preference disappeared after 4 consecutive check-ups, with no sex-related interference. For further validation of visually-cued operant conditioning paradigm, drugs MK-801 (dizocilpine) and caffeine, known to affect performance in learning tasks, were administered intraperitoneally. Chronic MK-801 (0.17 mg/kg) impaired maze learning, resulting in no color preference development. Conversely, caffeine administration enhanced test performance, increasing precision in fish. This developed paradigm offers a viable approach for studying learning and memory and presents an effective alternative to rodent-based drug screening tools, exhibiting good face and predictive validity. [ABSTRACT FROM AUTHOR]

Chronodisruption caused by factors such as light at night and mistimed meals has been linked to numerous physiological alterations in vertebrates and may be an anxiogenic factor affecting welfare. This study aims to investigate whether chronodisruption causes measurable changes in the anxiety responses of goldfish under two conditions: randomly scheduled feeding (RF) and continuous light (LL). Anxiety-like behavior was assessed in the open field with object approach and black/white preference tests, which had been validated using diazepam. An increased thigmotaxis response and decreased object exploration under both chronodisruption protocols indicated anxiety states. Furthermore, locomotor activity was increased in LL fish. The black/white preference test discriminated anxiolysis induced by diazepam but was unable to detect anxiety caused by chronodisruption. Plasma cortisol increased in both RF and LL fish throughout the experiment, confirming that both conditions caused stress. The LL fish also showed an apparently desensitized hypothalamus–pituitary–interrenal HPI axis, with a decrease in pomc and crf expression. Individual analysis found no correlation between anxiety-like behavior and stress axis activation nor between scototaxis and thigmotaxis responses. However, individual differences in sensitivity to each test were detected. Altogether, these results highlight circadian disruption as a stressor for fish and endorse a multiple variable approach for reliably assessing animal discomfort.

Motivation can be defined as a function that activates and directs the behavior toward goals. In neuropsychiatric conditions, motivation deficits such as apathy are frequent and interfere with treatment observance and clinical outcome. The current standard approach is to assess motivation deficits with subjective questionnaires that depend on patients’ insight and provide no information about underlying pathophysiological mechanisms. Here, I present a novel approach that consists in fitting computational models to the behavior observed in objective tests, so as to infer parameters that specify the patient’s motivational state. These computational parameters provide (1) an explanation at the cognitive level (e.g., reduced sensitivity to reward), (2) a dysfunction at the neural level (e.g., altered dopamine release) and (3) a prediction of treatment outcome (e.g., improvement with psychostimulants). Computational fingerprinting may therefore pave the way toward a more personalized medicine.

Objective: To investigate the P-SOD's effects on behavior and cerebral oxidative stress in AD mice, and to analyze the relationship between changes in mouse behavior and levels of brain oxidation and antioxidant. Methods: 32 KM male mice were used for adaptive breeding for 7 days. The mice were randomly divided into 4 groups: sham operation group (group S), model group (group M), SOD intervention model group (group SM), and P-SOD intervention model group (group PM). After 7 days normal feeding for adaptation, mice from these four groups were intraperitoneally injected daily for 14 days: group S and M with normal saline; group SM with 6 mg/kg SOD, group PM with 6 mg/kg pETl6b-PTD4-Cu, Zn-SOD. On the 8th day of intraperitoneal injection, after locating the right lateral ventricle of mice by the stereotaxic apparatus, 2 滋L of normal saline was injected into lateral ventricle in mice from group S, whereas 2 滋L of A茁1-42 oligomer (1 滋g/mL) was injected into lateral ventricle in mice from other groups. The Y-maze and the light-dark box test performed on the 8th, 24th and 31st day respectively. After the behavior test, animals were sacrificed and the fresh tissue of one cerebral hemisphere was taken for SOD and MDA determination. Resutls: 1) Behavioral tests: There was no statistical difference in distance, duration and numbers of visits in novel arm of Y-maze test and in light box of Light-dark box test between mice from different groups on the 8th day. However, on the 24th and 31th day, mice in group M showed significantly increased with those above when compared with the group S (P<0.05). Differently, mice in group PM showed significantly decreased with those above when compared with those from group M (P<0.05). 2) Compared with group M, mice in group S and PM showed significantly higher SOD but lower MDA levels in brain tissue (P<0.05). 3) Correlation analysis between SOD/MDA expression and behavioral performance showed SOD levels negatively, whereas MDA positively correlated with visiting distance, number and duration in Y-maze novel arm and light box. Conclusion: P-SOD intraperitoneal injection can alleviate A茁+-induced oxidative stress and improve behavioral deterioration in AD mice. The antioxidant function of P-SOD may be an effective method to prevent AD. [ABSTRACT FROM AUTHOR]

The radial arm maze (RAM) is a common behavioral test to quantify spatial learning and memory in rodents. Prior attempts to refine the standard experimental setup have been insufficient. Previously, we demonstrated the feasibility of a fully automated, voluntary, and stress-free eight-arm RAM not requiring food or water deprivation. Here, we compared this newly developed refined RAM to a classic manual experimental setup using 24 female 10-12 weeks old C57BL/6J mice. We used a lipopolysaccharide (LPS)-induced model of systemic inflammation to examine long-term cognitive impairment for up to 13 weeks following LPS injection. Both mazes demonstrated robust spatial learning performance during the working memory paradigm. The refined RAM detected spatial learning and memory deficits among LPS-treated mice in the working memory paradigm, whereas the classic RAM detected spatial learning and memory deficits only in the combined working/reference memory paradigm. In addition, the refined RAM allowed for quantification of an animal's overall exploratory behavior and day/night activity pattern. While our study highlights important aspects of refinement of the new setup, our comparison of methods suggests that both RAMs have their respective merits depending on experimental requirements. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) triggers a plethora of inflammatory events in the brain that aggravate secondary injury and impede tissue repair. Resident microglia (Mi) and blood-borne infiltrating macrophages (MΦ) are major players of inflammatory responses in the post-TBI brain and possess high functional heterogeneity. However, the plasticity of these cells has yet to be exploited to develop therapies that can mitigate brain inflammation and improve the outcome after TBI. This study investigated the transcription factor STAT1 as a key determinant of proinflammatory Mi/MΦ responses and aimed to develop STAT1 as a novel therapeutic target for TBI using a controlled cortical impact model of TBI on adult male mice. TBI induced robust upregulation of STAT1 in the brain at the subacute injury stage, which occurred primarily in Mi/MΦ. Intraperitoneal administration of fludarabine, a selective STAT1 inhibitor, markedly alleviated proinflammatory Mi/MΦ responses and brain inflammation burden after TBI. Such phenotype-modulating effects of fludarabine on post-TBI Mi/MΦ were reproduced by tamoxifen-induced, selective KO of STAT1 in Mi/MΦ (STAT1 mKO). By propelling Mi/MΦ away from a detrimental proinflammatory phenotype, STAT1 mKO was sufficient to reduce long-term neurologic deficits and brain lesion size after TBI. Importantly, short-term fludarabine treatment after TBI elicited long-lasting improvement of TBI outcomes, but this effect was lost on STAT1 mKO mice. Together, our study provided the first line of evidence that STAT1 causatively determines the proinflammatory phenotype of brain Mi/MU after TBI. We also showed promising preclinical data supporting the use of fludarabine as a novel immunomodulating therapy to TBI. [ABSTRACT FROM AUTHOR]

Neurodevelopmental disorders (NDDs) are complex disorders which can be associated with many comorbidities and exhibit multifactorial-dependent phenotypes. An important characteristic is represented by the early onset of the symptoms, during childhood or young adulthood, with a great impact on the socio-cognitive functioning of the affected individuals. Thus, the aim of our review is to describe and to argue the necessity of early developmental stages zebrafish models, focusing on NDDs, especially autism spectrum disorders (ASD) and also on schizophrenia. The utility of the animal models in NDDs or schizophrenia research remains quite controversial. Relevant discussions can be opened regarding the specific characteristics of the animal models and the relationship with the etiologies, physiopathology, and development of these disorders. The zebrafish models behaviors displayed as early as during the pre-hatching embryo stage (locomotor activity prone to repetitive behavior), and post-hatching embryo stage, such as memory, perception, affective-like, and social behaviors can be relevant in ASD and schizophrenia research. The neurophysiological processes impaired in both ASD and schizophrenia are generally highly conserved across all vertebrates. However, the relatively late individual development and conscious social behavior exhibited later in the larval stage are some of the most important limitations of these model animal species. [ABSTRACT FROM AUTHOR]

Cannabidiol (CBD) presents antiparkinsonian properties and neuromodulatory effects, possibly due to the pleiotropic activity caused at multiple molecular targets. Recently, the GPR55 receptor has emerged as a molecular target of CBD. Interestingly, GPR55 mRNA is expressed in the external globus pallidus (GPe) and striatum, hence, it has been suggested that its activity is linked to motor dysfunction in Parkinson's disease (PD). The present study aimed to evaluate the effect of the intrapallidal injection of both CBD and a selective GPR55 antagonist (CID16020046) on motor asymmetry, fine motor skills, and GAD-67 expression in hemiparkinsonian rats. The hemiparkinsonian animal model applied involved the induction of a lesion in male Wistar rats via the infusion of the neurotoxin 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle via stereotaxic surgery. After a period of twenty days, a second surgical procedure was performed to implant a guide cannula into the GPe. Seven days later, lysophosphatidylinositol (LPI), CBD, or CID16020046 were injected once a day for three consecutive days (from the 28th to the 30th day post-lesion). Amphetamine-induced turning behavior was evaluated on the 14th and 30th days post-injury. The staircase test and fine motor skills were evaluated as follows: the rats were subject to a ten-day training period prior to the 6-OHDA injury; from the 15th to the 19th days postlesion, the motor skills alterations were evaluated under basal conditions; and, from the 28th to the 30th day post-lesion, the pharmacological effects of the drugs administered were evaluated. The results obtained show that the administration of LPI or CBD generated lower levels of motor asymmetry in the turning behavior of hemiparkinsonian rats. It was also found that the injection of CBD or CID16020046, but not LPI, in the hemiparkinsonian rats generated significantly superior performance in the staircase test, in terms of the use of the forelimb contralateral to the 6-OHDA-induced lesion, when evaluated from the 28th to the 30th day post-lesion. Similar results were also observed for superior fine motor skills performance for pronation, grasp, and supination. Finally, the immunoreactivity levels were found to decrease for the GAD-67 enzyme in the striatum and the ipsilateral GPe of the rats injected with CBD and CID16020046, in contrast with those lesioned with 6-OHDA. The results obtained suggest that the inhibitory effects of CBD and CID16020046 on GPR55 in the GPe could be related to GABAergic overactivation in hemiparkinsonism, thus opening new perspectives to explain, at a cellular level, the reversal of the motor impairment observed in PD models. [ABSTRACT FROM AUTHOR]