Behavioral And Brain Functions[JOURNAL]
Sun
200 papers
Sex differences in reward-based operant conditioning performance and neurotransmitter changes following chronic sleep restriction stress in rats.
Zhang Y, Chen F, Yu M … +5 more , Li Y, Chen S, Choudhary MI, Liu X, Jiang N
Behav Brain Funct · 2025 Feb · PMID 40022197 · Full text
BACKGROUND: Sleep deprivation significantly impairs cognitive function, which disrupts daily life. However, sex differences in these impairments are not well understood, as most preclinical studies primarily use male ani...
BACKGROUND: Sleep deprivation significantly impairs cognitive function, which disrupts daily life. However, sex differences in these impairments are not well understood, as most preclinical studies primarily use male animals, neglecting potential differences between sexes. This study aims to investigate sex-specific differences in cognitive function under sleep deprivation using reward-based operant conditioning tasks. RESULTS: Sprague-Dawley rats were pre-trained on a lever-press task and subsequently divided into control and chronic sleep restriction (CSR) groups. The CSR group underwent 14 days of sleep restriction. After CSR modeling, rats were assessed using the open field test, retraining on the lever-pressing task, signal discrimination task, and extinction task to evaluate motor abilities, memory formation, learning, and cognitive flexibility. CSR significantly impaired task performance in both sexes, with rats requiring more time and exhibiting lower accuracy. In the signal discrimination task, male rats showed longer feeding latency and lower accuracy compared to females. CSR also specifically increased the frequency of operant responses in male rats. In the extinction task, CSR enhanced exploration time and frequency in both sexes, with females exhibiting significantly higher exploration frequencies than males. Biochemically, CSR induced sex-specific alterations, including elevated serum MDA and MAO levels in males and increased serotonin, dopamine, and epinephrine in both sexes. Although activation was observed in metabolites of the tryptophan-kynurenine pathway, sex differences were evident in the kynurenic acid metabolism levels in the prefrontal cortex. CONCLUSIONS: CSR impairs cognitive function in both male and female rats, with significant sex differences observed. Male CSR rats exhibited impaired signal discrimination, while CSR impaired extinction learning in female rats. These impairments are accompanied by CSR-induced oxidative stress, neurotransmitter dysregulation, and disturbances in the tryptophan metabolic pathway. These findings underscore the importance of considering sex differences in understanding the effects of sleep deprivation on cognitive function and developing targeted intervention strategies.
Fecal microbiota transplantation attenuates Alzheimer's disease symptoms in APP/PS1 transgenic mice via inhibition of the TLR4-MyD88-NF-κB signaling pathway-mediated inflammation.
Li X, Ding Q, Wan X … +3 more , Wu Q, Ye S, Lou Y
Behav Brain Funct · 2025 Jan · PMID 39780269 · Full text
Alzheimer's disease (AD) is a prevalent and progressive neurodegenerative disorder that is the leading cause of dementia. The underlying mechanisms of AD have not yet been completely explored. Neuroinflammation, an infla...
Alzheimer's disease (AD) is a prevalent and progressive neurodegenerative disorder that is the leading cause of dementia. The underlying mechanisms of AD have not yet been completely explored. Neuroinflammation, an inflammatory response mediated by certain mediators, has been exhibited to play a crucial role in the pathogenesis of AD. Additionally, disruption of the gut microbiota has been found to be associated with AD, and fecal microbiota transplantation (FMT) has emerged as a potential therapeutic approach. However, the precise mechanism of FMT in the treatment of AD remains elusive. In this study, FMT was performed by transplanting fecal microbiota from healthy wild-type mice into APP/PS1 mice (APPswe, PSEN1dE9) to assess the effectiveness of FMT in mitigating AD-associated inflammation and to reveal its precise mechanism of action. The results demonstrated that FMT treatment improved cognitive function and reduced the expression levels of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway in mice, which was accompanied by the restoration of gut microbial dysbiosis. These findings suggest that FMT has the potential to ameliorate AD symptoms and delay the disease progression in APP/PS1 mice.
Host genetics maps to behaviour and brain structure in developmental mice.
Asbury S, Lai JKY, Rilett KC … +5 more , Haqqee Z, Darwin BC, Ellegood J, Lerch JP, Foster JA
Behav Brain Funct · 2025 Jan · PMID 39748372 · Full text
Gene-environment interactions in the postnatal period have a long-term impact on neurodevelopment. To effectively assess neurodevelopment in the mouse, we developed a behavioural pipeline that incorporates several valida...
Gene-environment interactions in the postnatal period have a long-term impact on neurodevelopment. To effectively assess neurodevelopment in the mouse, we developed a behavioural pipeline that incorporates several validated behavioural tests to measure translationally relevant milestones of behaviour in mice. The behavioral phenotype of 1060 wild type and genetically-modified mice was examined followed by structural brain imaging at 4 weeks of age. The influence of genetics, sex, and early life stress on behaviour and neuroanatomy was determined using traditional statistical and machine learning methods. Analytical results demonstrated that neuroanatomical diversity was primarily associated with genotype whereas behavioural phenotypic diversity was observed to be more susceptible to gene-environment variation. We describe a standardized mouse phenotyping pipeline, termed the Developmental Behavioural Milestones (DBM) Pipeline released alongside the 1000 Mouse Developmental Behavioural Milestones (1000 Mouse DBM) database to institute a novel framework for reproducible interventional neuroscience research.
Can rewards enhance creativity? Exploring the effects of real and hypothetical rewards on creative problem solving and neural mechanisms.
Cui C, Yuan Y, Jiang Y
Behav Brain Funct · 2024 Dec · PMID 39732718 · Full text
Reward cues have long been considered to enhance creative performance; however, little is known about whether rewards can affect creative problem solving by manipulating states of flexibility and persistence. This study...
Reward cues have long been considered to enhance creative performance; however, little is known about whether rewards can affect creative problem solving by manipulating states of flexibility and persistence. This study sought to elucidate the differential impacts of real versus hypothetical rewards on the creative process utilizing the Chinese compound remote association task. Behavioral analysis revealed a significantly enhanced solution rate and response times in scenarios involving real rewards, in contrast to those observed with hypothetical rewards. Electrophysiological findings indicated that hypothetical rewards led to more positive P200-600 amplitudes, in stark contrast to the amplitudes observed in the context of real rewards. These findings indicate a positive impact of real rewards on creative remote associations and contribute new insights into the relationship between rewards and creative problem solving, highlighting the crucial role of persistence/flexibility in the formation of creativity.
Altered trial-to-trial responses to reward outcomes in KCNMA1 knockout mice during probabilistic learning tasks.
Ohta H, Nozawa T, Higuchi K … +4 more , Meredith AL, Morimoto Y, Satoh Y, Ishizuka T
Behav Brain Funct · 2024 Dec · PMID 39731174 · Full text
The large-conductance calcium- and voltage-activated potassium (BK) channels, encoded by the KCNMA1 gene, play important roles in neuronal function. Mutations in KCNMA1 have been found in patients with various neurodevel...
The large-conductance calcium- and voltage-activated potassium (BK) channels, encoded by the KCNMA1 gene, play important roles in neuronal function. Mutations in KCNMA1 have been found in patients with various neurodevelopmental features, including intellectual disability, autism spectrum disorder (ASD), or attention deficit hyperactivity disorder (ADHD). Previous studies of KCNMA1 knockout mice have suggested altered activity patterns and behavioral flexibility, but it remained unclear whether these changes primarily affect immediate behavioral adaptation or longer-term learning processes. Using a 5-armed bandit task (5-ABT) and a novel Δrepeat rate analysis method that considers individual baseline choice tendencies, we investigated immediate trial-by-trial Win-Stay-Lose-Shift (WSLS) strategies and learning rates across multiple trials in KCNMA1 knockout (KCNMA1) mice. Three key findings emerged: (1) Unlike wildtype mice, which showed increased Δrepeat rates after rewards and decreased rates after losses, KCNMA1 mice exhibited impaired WSLS behavior, (2) KCNMA1 mice displayed shortened response intervals after unrewarded trials, and (3) despite these short-term behavioral impairments, their learning rates and task accuracy remained comparable to wildtype mice, with significantly shorter task completion times. These results suggest that BK channel dysfunction primarily alters immediate behavioral responses to outcomes in the next trial rather than affecting long-term learning capabilities. These findings and our analytical method may help identify behavioral phenotypes in animal models of both BK channel-related and other neurodevelopmental disorders.
From controllers to cognition: the importance of selection factors on video game and gameplay mechanic-derived cognitive differences.
Vo TT, Pahlen S, Zheng A … +7 more , Yu S, Lor E, Bowman ND, Corley RP, Friedman NP, Wadsworth SJ, Reynolds CA
Behav Brain Funct · 2024 Dec · PMID 39707528 · Full text
Playing video games, especially games with action-based mechanics, is correlated with better cognitive performance, yet these performance advantages may originate from intrinsic factors such as earlier life cognitive dif...
Playing video games, especially games with action-based mechanics, is correlated with better cognitive performance, yet these performance advantages may originate from intrinsic factors such as earlier life cognitive differences. We investigated whether gaming-cognition associations in a sample past young adulthood remain robust after accounting for adolescent cognitive functioning. Using data from the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife; N = 1241, M = 33.3, %, age range = 28-51, Female = 52.9%), we compared cognitive performance of adult recreational gamers (40.6%) to non-gamers (59.4%) and between different types of gamers. Measures included processing speed, spatial reasoning, and working memory cognitive tasks, gaming status, and gameplay type engagement. The majority of gamer participants reported exclusively playing puzzle/strategy/life simulation games (53.0%) or action type games (33.1%); a smaller proportion reported playing both types of games (10.3%). Overall, gamers significantly outperformed non-gamers across most cognitive tasks (Cohen's d = 0.17-0.25), with limited evidence of a differential gameplay mechanic effect across tasks. Selection effects were evident whereby after adolescent IQ adjustment, gamer cognitive effects diminished by over 35% but persisted for spatial performance. Adolescent IQ predicted puzzle/strategy/life simulation preference but not action-type games, suggesting a selection effect. Our study replicates prior gaming findings and reveals that earlier life functioning contributes to adult gaming-cognition associations. Gamer-spatial associations are not fully attributable to intrinsic factors, and playing video games, regardless of a specific gameplay mechanic or genre, may represent a cognitively engaging lifestyle behavior that may benefit cognitive functioning, with implications for preserved cognition.
Characterization of neuronal oscillations in the prelimbic cortex, nucleus accumbens and CA1 hippocampus during object retrieval task in rats predisposed to early life stress.
Sharma SS, Sasidharan A, Yoganarasimha D … +1 more , Laxmi TR
Behav Brain Funct · 2024 Dec · PMID 39696528 · Full text
BACKGROUND: Early life stress (ELS) during the stress hypo-responsive period (SHRP) alters the curiosity-like behavior later during adolescence. Previous studies have shown maternal separation (MS) stress-induced heighte...
BACKGROUND: Early life stress (ELS) during the stress hypo-responsive period (SHRP) alters the curiosity-like behavior later during adolescence. Previous studies have shown maternal separation (MS) stress-induced heightened curiosity and associated risk-taking behavior in the object retrieval task (ORT). However, the neural correlates of curiosity in adolescent rats predisposed to early life stress remain unexplored. Hence, the present study aimed to investigate the neural oscillatory patterns and network characteristics in the regions implicated in curiosity behavior, such as the Prelimbic cortex (PL), Nucleus Accumbens (NAc), and CA1 of the Hippocampus. The local field potentials data were analysed to understand the neural activity patterns in these areas during the risky zone crossing and object retrieval phase of the ORT in MS rats and compared with the normal control (NC) group. RESULTS: In comparison to NC, MS rats showed a reduction in the theta power at 8-12 Hz, beta power at 12-20 Hz, and gamma power at 20-40 Hz range in the PL during risky zone crossing time. MS rats also showed reduced cross-correlation between PL-CA1 and reduced theta coherence between NAc-CA1 during risky zone crossing. During the object retrieval phase, the MS rats showed reduced peak cross-correlation between PL-CA1 and PL-NAc. Behaviourally, MS rats displayed an increased preference for the curiosity platform and retrieved more hidden objects, thus accounting for a higher curiosity index than controls. CONCLUSION: In summary, a reduced synchronization between the PL, NAc, and CA1 during the object retrieval task indicates how early MS stress during a critical developmental period impacts the limbic circuit connectivity. This corresponded with enhanced curiosity index in adolescent MS rats, predicting an altered intrinsic motivation and hence a higher susceptibility to substance use disorders during adolescence.
Retraction Note: 4'‑O‑β‑D‑glucosyl‑5‑O‑methylvisamminol, an active ingredient of Saposhnikovia divaricata, attenuates high‑mobility group box 1 and subarachnoid hemorrhage‑induced vasospasm in a rat model.
Chang CZ, Wu SC, Kwan AL … +1 more , Lin CL
Behav Brain Funct · 2024 Dec · PMID 39668363 · Full text
Abstract loading — click title to view on PubMed.
Uncovering hidden prosocial behaviors underlying aggression motivation in mice and young children.
Lee CL, Su YS, Chang CY … +7 more , Kung TY, Ma YK, Zeng PY, Cheng CC, Chang YJ, Chou YJ, Kuo TH
Behav Brain Funct · 2024 Nov · PMID 39609920 · Full text
BACKGROUND: Animals exhibit a wide range of social behaviors, including positive actions that promote social cohesion and negative behaviors associated with asserting dominance. While these behaviors are often viewed as...
BACKGROUND: Animals exhibit a wide range of social behaviors, including positive actions that promote social cohesion and negative behaviors associated with asserting dominance. While these behaviors are often viewed as opposites, they can also exist independently or coexist in complex ways, necessitating further investigation into their interrelationships. RESULTS: To study the interplay between these two types of behaviors, we examined mouse social behaviors using resident-intruder assays and revealed a negative correlation between social aggression and prosocial allogrooming. Suppressing aggressive motivation through various manipulations, including social subordination, olfaction ablation, and inhibition of aggressive neural circuits, led to an increased display of allogrooming behavior. The mouse findings prompted us to further explore the relationship between aggression and prosocial behaviors in preschool children. Similarly, we observed a negative association between aggression and prosocial behaviors, which were potentially influenced by their inhibitory control abilities. CONCLUSIONS: Through this cross-species study, we uncovered the inhibitory impact of aggressive neural circuits on mouse allogrooming and established a link between aggression and prosocial behaviors in children. These insights offer valuable implications for understanding and potentially influencing social interactions in both animal and human contexts, with potential applications in preschool education practices.
Loss of the zinc receptor ZnR/GPR39 in mice enhances anxiety-related behavior and motor deficits, and modulates KCC2 expression in the amygdala.
Sagi R, Chakraborty M, Bogdanovic M … +5 more , Asraf H, Sekler I, Kofman O, Cohen H, Hershfinkel M
Behav Brain Funct · 2024 Nov · PMID 39581978 · Full text
BACKGROUND: Mood disorders, particularly depression and anxiety, are associated with zinc dyshomeostasis and aberrant GABAergic signaling. Activation of ZnR/GPR39 by synaptic zinc in the hippocampus triggers phosphorylat...
BACKGROUND: Mood disorders, particularly depression and anxiety, are associated with zinc dyshomeostasis and aberrant GABAergic signaling. Activation of ZnR/GPR39 by synaptic zinc in the hippocampus triggers phosphorylation of extracellular regulated kinase (ERK1/2), which regulates the K/Cl cotransporter (KCC2) and thereby GABAergic inhibitory neurotransmission and seizure activity. Therefore, we studied whether impaired ZnR/GPR39 signaling is linked to anxiety-related behavior in male or female mice. RESULTS: Using the acoustic startle response, elevated plus maze, and open field test, we found increased anxiety-related behavior in ZnR/GPR39 knockout (KO) mice. Despite a well-established sex difference, where females are typically more prone to anxiety, both male and female ZnR/GPR39 KO mice exhibited increased anxiety-related behavior compared to wildtype (WT) mice. Additionally, ZnR/GPR39 KO mice displayed impaired motor coordination in the pole and rotarod tests but did not show reduced muscle strength, as indicated by a grip test. Finally, we found intrinsic alterations in the expression level of KCC2, a major Cl transporter regulating GABAergic signaling, in the amygdala of naïve ZnR/GPR39 KO mice compared to controls. CONCLUSIONS: Our findings indicate that loss of ZnR/GPR39 enhances anxiety-related behavior in both male and female mice. Moreover, ZnR/GPR39 KO mice exhibit impaired motor coordination, which may be associated with increased anxiety. Finally, we demonstrate that loss of ZnR/GPR39 modulates the expression of KCC2 in the amygdala. Thus, we propose that ZnR/GPR39 can serve as a target for regulating GABAergic signaling in anxiety treatment.
Spectral tuning and after-effects in neural entrainment.
Menétrey MQ, Pascucci D
Behav Brain Funct · 2024 Nov · PMID 39574159 · Full text
Neural entrainment has become a popular technique to non-invasively manipulate brain rhythms via external, periodic stimulation. However, there is still debate regarding its underlying mechanisms and effects on brain act...
Neural entrainment has become a popular technique to non-invasively manipulate brain rhythms via external, periodic stimulation. However, there is still debate regarding its underlying mechanisms and effects on brain activity. Here, we used EEG recordings during a visual entrainment paradigm to assess characteristic changes in the spectral content of EEG signals due to entrainment. Our results demonstrate that entrainment not only increases synchrony between neural oscillations and the entraining stimulus but also elicits previously unreported spectral tuning effects and long-lasting after-effects. These findings offer compelling evidence for the presence of dedicated, flexible, and adaptive mechanisms for neural entrainment, which may have key roles in adjusting the sensitivity and dynamic range of brain oscillators in response to environmental temporal structures.
Cutibacterium Acnes induces Alzheimer's disease-like pathology in brains of wistar rats through structural changes associated with microtubules.
Aliashrafi M, Nasehi M, Siadat SD … +3 more , Mohammadi-Mahdiabadi-Hasani MH, Zali H, Niknam Z
Behav Brain Funct · 2024 Nov · PMID 39574154 · Full text
BACKGROUND: Cutibacterium acnes(C. acnes), a Gram-positive anaerobe and a dominant bacterium species in the sebaceous follicles of the face was detected in the brain of Alzheimer's disease (AD) patients. It has been foun...
BACKGROUND: Cutibacterium acnes(C. acnes), a Gram-positive anaerobe and a dominant bacterium species in the sebaceous follicles of the face was detected in the brain of Alzheimer's disease (AD) patients. It has been found that C. acnes activates non-specifically the innate immune system by producing proinflammatory cytokines and can participate in brain inflammation. We hypothesise that C. acnes could influence the brain through the structural alteration in axons and dendrites of neurons. METHODS: In this regard, the hippocampus of rats was infected with C. acnes, and memory retention, amyloid-β (Aβ) deposition, hyperphosphorylated tau protein (p-Tau) formation, and expression levels of MAP2 and β-tubulin proteins in the hippocampus tissues were investigated. RESULTS: C. acnes-infected rats displayed memory deficits and Aβ deposits were detected in their hippocampus tissue up to 7 days post-infection. C. acnes was neurotoxic and exerted detrimental effects on MAP2 and β-tubulin proteins, which are required for normal neuronal function. An elevated level of p-Tau was also identified in infected animals. CONCLUSION: Based on these results, we propose that C. acnes infection of the brain participates in the initiation of the pathogenesis of sporadic AD through degeneration of axons and dendrites.
Investigation in the cannabigerol derivative VCE-003.2 as a disease-modifying agent in a mouse model of experimental synucleinopathy.
Burgaz S, Navarro E, Rodríguez-Carreiro S … +7 more , Navarrete C, Garrido-Rodríguez M, Lastres-Becker I, Chocarro J, Lanciego JL, Muñoz E, Fernández-Ruiz J
Behav Brain Funct · 2024 Nov · PMID 39487447 · Full text
BACKGROUND: The cannabigerol derivative VCE-003.2, which has activity at the peroxisome proliferator-activated receptor-γ has afforded neuroprotection in experimental models of Parkinson's disease (PD) based on mitochond...
BACKGROUND: The cannabigerol derivative VCE-003.2, which has activity at the peroxisome proliferator-activated receptor-γ has afforded neuroprotection in experimental models of Parkinson's disease (PD) based on mitochondrial dysfunction (6-hydroxydopamine-lesioned mice) and neuroinflammation (LPS-lesioned mice). Now, we aim to explore VCE-003.2 neuroprotective properties in a PD model that also involves protein dysregulation, other key event in PD pathogenesis. METHODS: To this end, an adeno-associated viral vector serotype 9 coding for a mutated form of the α-synuclein gene (AAV9-SynA53T) was unilaterally delivered in the substantia nigra pars compacta (SNpc) of mice. This model leads to motor impairment and progressive loss of tyrosine hydroxylase-labelled neurons in the SNpc. RESULTS: Oral administration of VCE-003.2 at 20 mg/kg for 14 days improved the performance of mice injected with AAV9-SynA53T in various motor tests, correlating with the preservation of tyrosine hydroxylase-labelled neurons in the SNpc. VCE-003.2 also reduced reactive microgliosis and astrogliosis in the SNpc. Furthermore, we conducted a transcriptomic analysis in the striatum of mice injected with AAV9-SynA53T and treated with either VCE-003.2 or vehicle, as well as control animals. This analysis aimed to identify gene families specifically altered by the pathology and/or VCE-003.2 treatment. Our data revealed pathology-induced changes in genes related to mitochondrial function, lysosomal cell pathways, immune responses, and lipid metabolism. In contrast, VCE-003.2 treatment predominantly affected the immune response through interferon signaling. CONCLUSION: Our study broadens the neuroprotective potential of VCE-003.2, previously described against mitochondrial dysfunction, oxidative stress, glial reactivity and neuroinflammation in PD. We now demonstrate its efficacy against another key pathogenic event in PD as α-synuclein dysregulation. Furthermore, our investigation sheds light on the molecular mechanisms underlying VCE-003.2 revealing its role in regulating interferon signaling. These findings, together with a favorable ADMET profile, enhance the preclinical interest of VCE-003.2 towards its future clinical development in PD.
Cofilin linked to GluN2B subunits of NMDA receptors is required for behavioral sensitization by changing the dendritic spines of neurons in the caudate and putamen after repeated nicotine exposure.
Kim S, Sohn S, Choe ES
Behav Brain Funct · 2024 Oct · PMID 39402674 · Full text
BACKGROUND: Nicotine dependence is associated with glutamatergic neurotransmission in the caudate and putamen (CPu) of the forebrain which includes alterations in the structure of dendritic spines at glutamate synapses....
BACKGROUND: Nicotine dependence is associated with glutamatergic neurotransmission in the caudate and putamen (CPu) of the forebrain which includes alterations in the structure of dendritic spines at glutamate synapses. These changes after nicotine exposure can lead to the development of habitual behaviors such as smoking. The present study investigated the hypothesis that cofilin, an actin-binding protein that is linked to the GluN2B subunits of N-methyl-D-aspartate (NMDA) receptors regulates the morphology of dendritic spines in the neurons of the CPu after repeated exposure to nicotine. RESULTS: Adult male rats received subcutaneous injections of nicotine (0.3 mg/kg/day) or vehicle for seven consecutive days. DiI staining was conducted to observe changes in dendritic spine morphology. Repeated subcutaneous injections of nicotine decreased the phosphorylation of cofilin while increasing the formation of thin spines and filopodia in the dendrites of medium spiny neurons (MSN) in the CPu of rats. Bilateral intra-CPu infusion of the cofilin inhibitor, cytochalasin D (12.5 µg/µL/side), restored the thin spines and filopodia from mushroom types after repeated exposure to nicotine. Similar results were obtained from the bilateral intra-CPu infusion of the selective GluN2B subunit antagonist, Ro 25-6981 (4 µM/µL/side). Bilateral intra-CPu infusion of cytochalasin D that interferes with the actin-cofilin interaction attenuated the repeated nicotine-induced increase in locomotor sensitization in rats. CONCLUSIONS: These findings suggest that active cofilin alters the structure of spine heads from mushroom to thin spine/filopodia by potentiating actin turnover, contributing to behavioral sensitization after nicotine exposure.
Comparative effect of atorvastatin and risperidone on modulation of TLR4/NF-κB/NOX-2 in a rat model of valproic acid-induced autism.
Farrag EAE, Askar MH, Abdallah Z … +9 more , Mahmoud SM, Abdulhai EA, Abdelrazik E, Nashar EME, Alasiri FM, Alqahtani ANS, Eldesoqui M, Eldib AM, Magdy A
Behav Brain Funct · 2024 Sep · PMID 39350139 · Full text
BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that is significantly increasing, resulting in severe distress. The approved treatment for ASD only partially improves the sympoms, but...
BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that is significantly increasing, resulting in severe distress. The approved treatment for ASD only partially improves the sympoms, but it does not entirely reverse the symptoms. Developing novel disease-modifying drugs is essential for the continuous improvement of ASD. Because of its pleiotropic effect, atorvastatin has been garnered attention for treating neuronal degeneration. The present study aimed to investigate the therapeutic effects of atorvastatin in autism and compare it with an approved autism drug (risperidone) through the impact of these drugs on TLR4/NF-κB/NOX-2 and the apoptotic pathway in a valproic acid (VPA) induced rat model of autism. METHODS: On gestational day 12.5, pregnant rats received a single IP injection of VPA (500 mg/kg), for VPA induced autism, risperidone and atorvastatin groups, or saline for control normal group. At postnatal day 21, male offsprings were randomly divided into four groups (n = 6): control, VPA induced autism, risperidone, and atorvastatin. Risperidone and atorvastatin were administered from postnatal day 21 to day 51. The study evaluated autism-like behaviors using the three-chamber test, the dark light test, and the open field test at the end of the study. Biochemical analysis of TLR4, NF-κB, NOX-2, and ROS using ELISA, RT-PCR, WB, histological examination with hematoxylin and eosin and immunohistochemical study of CAS-3 were performed. RESULTS: Male offspring of prenatal VPA-exposed female rats exhibited significant autism-like behaviors and elevated TLR4, NF-κB, NOX-2, ROS, and caspase-3 expression. Histological analysis revealed structural alterations. Both risperidone and atorvastatin effectively mitigated the behavioral, biochemical, and structural changes associated with VPA-induced rat model of autism. Notably, atorvastatin group showed a more significant improvement than risperidone group. CONCLUSIONS: The research results unequivocally demonstrated that atorvastatin can modulate VPA-induced autism by suppressing inflammation, oxidative stress, and apoptosis through TLR4/NF-κB/NOX-2 signaling pathway. Atorvastatin could be a potential treatment for ASD.
Assessing sociability using the Three-Chamber Social Interaction Test and the Reciprocal Interaction Test in a genetic mouse model of ASD.
Szabó J, Renczés E, Borbélyová V … +2 more , Ostatníková D, Celec P
Behav Brain Funct · 2024 Sep · PMID 39342245 · Full text
Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders with heterogeneous symptomatology. Arguably, the most pervasive shortfall of ASD are the deficits in sociability and the animal models of the diso...
Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders with heterogeneous symptomatology. Arguably, the most pervasive shortfall of ASD are the deficits in sociability and the animal models of the disorder are expected to exhibit such impairments. The most widely utilized behavioral task for assessing sociability in rodents is the Three-Chamber Social Interaction Test (SIT). However, SIT has been yielding inconsistent results in social interaction behavior across different rodent models of ASD, which could be pointing to the suboptimal methodology of the task. Here, we compared social behavior assessed in SIT and in another prominent sociability behavioral assay, Reciprocal Interaction Test (RCI), in a SH3 and multiple ankyrin repeated domains 3 (SHANK3) mouse model of ASD. Head-to-head comparison showed no association (p = 0.15, 0.25, 0.43) and a fixed bias (p = 0.01, < 0.001, < 0.001) in sociability assessment between the behavioral assays in both wild-type (WT) controls and Shank3B mice. Adult Shank3B mice of both sexes displayed normative sociability in SIT when compared to the WT controls (p = 0.74) but exhibited less than half of social interaction (p < 0.001) and almost three times more social disinterest (p < 0.001) when compared to WT mice in RCI. At least in the Shank3B mouse model of ASD, we presume RCI could be a preferable way of assessing social interaction compared to SIT. Considering the variability of animal models of ASD and the wide palette of tools available for the assessment of their behavior, a consensus approach would be needed for observational and interventional analyses.
Paternal preconception donepezil exposure enhances learning in offspring.
Fan G, Pan T, Ji X … +5 more , Jiang C, Wang F, Liu X, Ma L, Le Q
Behav Brain Funct · 2024 Sep · PMID 39342229 · Full text
BACKGROUND: Recent research has indicated that parental use of central nervous system-targeting medications during periconceptional periods may affect offspring across various developmental and behavioral domains. The pr...
BACKGROUND: Recent research has indicated that parental use of central nervous system-targeting medications during periconceptional periods may affect offspring across various developmental and behavioral domains. The present study sought to investigate the potential influence of paternal use of donepezil, a specific reversible central acetylcholinesterase inhibitor that activates the cholinergic system to promote cognition, on offspring. RESULTS: In this study, male rats were bred after 21 days of oral donepezil administration at a dose of 4 mg/kg to generate F1 offspring. Both male and female F₁ offspring displayed enhanced performance in learning and short-term memory tests, including novel object recognition, Y maze, and operant learning. Transcriptomic analysis revealed notable alterations in genes associated with the extracellular matrix in the hippocampal tissue of the F1 generation. Integration with genes related to intelligence identified potential core genes that may be involved in the observed behavioral enhancements. CONCLUSIONS: These findings indicate that prolonged paternal exposure to donepezil may enhance the learning and memory abilities of offspring, possibly by targeting nonneural, extracellular regions. Further research is required to fully elucidate any potential transgenerational effects.
Correction to: The vmPFC-IPL functional connectivity as the neural basis of future self-continuity impacted procrastination: the mediating role of anticipated positive outcomes.
Zhao X, Zhang R, Feng T
Behav Brain Funct · 2024 Sep · PMID 39261878 · Full text
Abstract loading — click title to view on PubMed.
MRS-assessed brain GABA modulation in response to task performance and learning.
Li H, Rodríguez-Nieto G, Chalavi S … +4 more , Seer C, Mikkelsen M, Edden RAE, Swinnen SP
Behav Brain Funct · 2024 Aug · PMID 39217354 · Full text
Gamma-aminobutyric acid (GABA), the most important inhibitory neurotransmitter in the human brain, has long been considered essential in human behavior in general and learning in particular. GABA concentration can be qua...
Gamma-aminobutyric acid (GABA), the most important inhibitory neurotransmitter in the human brain, has long been considered essential in human behavior in general and learning in particular. GABA concentration can be quantified using magnetic resonance spectroscopy (MRS). Using this technique, numerous studies have reported associations between baseline GABA levels and various human behaviors. However, regional GABA concentration is not fixed and may exhibit rapid modulation as a function of environmental factors. Hence, quantification of GABA levels at several time points during the performance of tasks can provide insights into the dynamics of GABA levels in distinct brain regions. This review reports on findings from studies using repeated measures (n = 41) examining the dynamic modulation of GABA levels in humans in response to various interventions in the perceptual, motor, and cognitive domains to explore associations between GABA modulation and human behavior. GABA levels in a specific brain area may increase or decrease during task performance or as a function of learning, depending on its precise involvement in the process under investigation. Here, we summarize the available evidence and derive two overarching hypotheses regarding the role of GABA modulation in performance and learning. Firstly, training-induced increases in GABA levels appear to be associated with an improved ability to differentiate minor perceptual differences during perceptual learning. This observation gives rise to the 'GABA increase for better neural distinctiveness hypothesis'. Secondly, converging evidence suggests that reducing GABA levels may play a beneficial role in effectively filtering perceptual noise, enhancing motor learning, and improving performance in visuomotor tasks. Additionally, some studies suggest that the reduction of GABA levels is related to better working memory and successful reinforcement learning. These observations inspire the 'GABA decrease to boost learning hypothesis', which states that decreasing neural inhibition through a reduction of GABA in dedicated brain areas facilitates human learning. Additionally, modulation of GABA levels is also observed after short-term physical exercise. Future work should elucidate which specific circumstances induce robust GABA modulation to enhance neuroplasticity and boost performance.
Social and emotional alterations in mice lacking the short dystrophin-gene product, Dp71.
Miranda R, Ceschi L, Le Verger D … +4 more , Nagapin F, Edeline JM, Chaussenot R, Vaillend C
Behav Brain Funct · 2024 Aug · PMID 39182120 · Full text
BACKGROUND: The Duchenne and Becker muscular dystrophies (DMD, BMD) are neuromuscular disorders commonly associated with diverse cognitive and behavioral comorbidities. Genotype-phenotype studies suggest that severity an...
BACKGROUND: The Duchenne and Becker muscular dystrophies (DMD, BMD) are neuromuscular disorders commonly associated with diverse cognitive and behavioral comorbidities. Genotype-phenotype studies suggest that severity and risk of central defects in DMD patients increase with cumulative loss of different dystrophins produced in CNS from independent promoters of the DMD gene. Mutations affecting all dystrophins are nevertheless rare and therefore the clinical evidence on the contribution of the shortest Dp71 isoform to cognitive and behavioral dysfunctions is limited. In this study, we evaluated social, emotional and locomotor functions, and fear-related learning in the Dp71-null mouse model specifically lacking this short dystrophin. RESULTS: We demonstrate the presence of abnormal social behavior and ultrasonic vocalization in Dp71-null mice, accompanied by slight changes in exploratory activity and anxiety-related behaviors, in the absence of myopathy and alterations of learning and memory of aversive cue-outcome associations. CONCLUSIONS: These results support the hypothesis that distal DMD gene mutations affecting Dp71 may contribute to the emergence of social and emotional problems that may relate to the autistic traits and executive dysfunctions reported in DMD. The present alterations in Dp71-null mice may possibly add to the subtle social behavior problems previously associated with the loss of the Dp427 dystrophin, in line with the current hypothesis that risk and severity of behavioral problems in patients increase with cumulative loss of several brain dystrophin isoforms.
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