Behavioral And Brain Functions[JOURNAL]
Sun
200 papers
Sex-specific neurological dysregulation may underpin distinctly different male and female behavioural phenotypes in a zebrafish model of autism spectrum disorder.
Pretorius L, Moodley T, Smith C
Behav Brain Funct · 2026 Jul · PMID 42402578 · Full text
BACKGROUND: Although distinctly different phenotypes of male and female autism spectrum disorder (ASD) have been long proposed, mechanistic insights are relatively lacking. Added complexities are that human ASD neurologi...
BACKGROUND: Although distinctly different phenotypes of male and female autism spectrum disorder (ASD) have been long proposed, mechanistic insights are relatively lacking. Added complexities are that human ASD neurological data has been predominantly generated in males, while behavioural observations are influenced by social norms. Using a preclinical in vivo model of idiopathic ASD, the current study may contribute to our understanding of the differences between the male and female ASD phenotype. METHODS: Briefly, ASD-like phenotype was induced in zebrafish embryos via valproate immersion. After confirmation of the larval phenotype, zebrafish were raised to adulthood to allow for sex-specific assessments. Adult behaviour was assessed in terms of anxiety (novel tank test), social interaction (social preference test) and aggression (mirror biting test). Behavioural data was interpreted in the context of whole brain proteome profiles obtained by untargeted proteomics. Differential protein expression analyses were performed using the Benjamini-Hochberg false discovery rate (significance at < 5%). In addition, main effects of ASD-like phenotype and sex were evaluated for specific neurotransmitter proteins. RESULTS: Behavioural data generally illustrated convergence of sexes in the ASD-like groups. For example, ASD-like males demonstrated a similar but exaggerated anxiety-like outcome, while ASD-like females exhibited behavioural responses more like control and ASD-like males within the social preference assay. Current data do not support aggressive behaviour as a hallmark of ASD in this model. In terms of neurotransmission profiles, significant sex-specific dysregulation was observed within the glutamatergic, GABAergic and dopaminergic systems. For example, greater excitation/inhibition imbalance was exhibited in ASD-like males vs. ASD-like females. Due to low abundance, data on the serotonergic system is less conclusive. CONCLUSION: Despite similar behavioural profiles, distinct neurotransmitter mechanisms elucidated may potentially warrant the consideration of sex-specific therapeutic targets in the ASD context.
The combined effects of probiotic and high-intensity interval training on memory function in high fat diet-fed rats.
Karami F, Shabkhiz F, Aadeli S … +5 more , Tamtaji OR, Aschner M, Halimi S, Fahanik Babaei J, Nabavizadeh F
Behav Brain Funct · 2026 Jul · PMID 42401969 · Full text
INTRODUCTION: This study aimed to investigate whether the probiotic Lactobacillus rhamnosus GG (LGG) (alone or combined with high-intensity interval training (HIIT)) could improve cognitive, electrophysiological changes,...
INTRODUCTION: This study aimed to investigate whether the probiotic Lactobacillus rhamnosus GG (LGG) (alone or combined with high-intensity interval training (HIIT)) could improve cognitive, electrophysiological changes, oxidative stress and metabolic parameters in HFD-fed rats. METHOD: Rats were randomly divided into four groups (n = 8): HFD group, HFD + LGG group, HFD+ HIIT group, and HFD + LGG+ HIIT group. Rats were fed HFD daily for a period of 16 weeks, during which LGG (1 × 10 colony forming unit (CFU)/ rats, orally), and HIIT protocol were administered four times a week on alternating days. At the end of study, assessment of social behavior, memory function, and Long-term potential (LTP) were performed using three-chambered apparatus, Y-maze task, and electrophysiology technique, respectively. Next, oxidative stress, lipid profiles, and liver enzymes were evaluated with routine kits. RESULTS: Both LGG and HIIT alone or in combination improved working memory, social memory, and LTP in HFD-fed rats. In addition, both LGG and HIIT alone or in combination increased the hippocampal levels of superoxide dismutase, catalase, and increased the serum levels of high-density lipoprotein (HDL), and decreased the serum levels of leptin, triglyceride, cholesterol, low-density lipoprotein (LDL), aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) in HFD-fed rats. CONCLUSIONS: The combination of LGG and HIIT provides a multi-pathway intervention that improves HFD-induced memory impairments by concurrently targeting oxidative stress, dyslipidemia, and hippocampal synaptic function. This supports the potential of combined lifestyle and microbiome-based therapies for preventing metabolic and cognitive disorders.
Impact of clomipramine postnatal exposure on sexual behavior and reproductive organs in female rats: role of sexual experience.
Molina-Jiménez T, Lozada NG, Alvarado M … +5 more , Juárez-Portilla C, Zepeda RC, Sánchez-Salcedo JA, Flores-Muñoz M, Bonilla-Jaime H
Behav Brain Funct · 2026 Jul · PMID 42399987 · Full text
Depression is a common psychiatric disorder during pregnancy and the postnatal period. Consequently, antidepressant treatment is primordial for the safety of the mother and the neonate. Clomipramine (CMI) is a tricyclic...
Depression is a common psychiatric disorder during pregnancy and the postnatal period. Consequently, antidepressant treatment is primordial for the safety of the mother and the neonate. Clomipramine (CMI) is a tricyclic antidepressant that has been prescribed even when the evidence suggests potential adverse effects on the neurodevelopment of the offspring, considering that antidepressant drugs can be transferred through breast milk. Nevertheless, in some cases, when the benefits outweigh the risks, it is used to treat severe depression in pregnant women. In rodents, postnatal administration of CMI causes persistent behavioral and neurophysiological alterations in adulthood. By contrast, a rewarding experience, such as mating, improves motivational and copulatory behavior in rodents through neuroplasticity in brain structures involved in reproduction. In a previous work, we reported that postnatal exposure to CMI disrupts the motivational and copulatory components of female sexual behavior during a single copulatory test. Therefore, the purpose of this study was to examine the effects of postnatal CMI treatment on female sexual behavior and reproductive tissues, and to determine whether sexual experience serves as a modulatory factor that ameliorates its potential impact on sexual performance. Female pups were divided in two groups, CMI group (30 mg/Kg) and the control group (NaCl 0.9%). Each group received a daily subcutaneous injection with CMI or saline solution from the 8th to 21st postnatal days. Behavioral test and histological analysis were performed at 3 months of age. The results indicated that postnatal CMI administration disrupts receptive but not proceptive behaviors. Repeated sexual encounters with males partially reversed the receptivity impairment in CMI-treated females, as it occurs in control rats. Histological data showed that CMI reduces the population of primordial and primary follicles; however, no morphological modifications were detected in the uterine layers. In conclusion, the data show that even when sexual experience partially improved copulatory behavior in female rats exposed to CMI during the postnatal period, ovarian development was affected, which could compromise fertility.
Postnatal relevance of HOXA5 transcription factor in cerebellum-associated behaviors and disorders.
Glibert H, Bridoux L, Moens C … +4 more , Olivier S, Jeannotte L, Clotman F, Gofflot F
Behav Brain Funct · 2026 Jul · PMID 42399966 · Full text
Hoxa5 encodes a transcription factor essential for embryonic patterning and organogenesis, with sustained expression in hindbrain precerebellar nuclei during postnatal development. Given prior evidence implicating HOXA5...
Hoxa5 encodes a transcription factor essential for embryonic patterning and organogenesis, with sustained expression in hindbrain precerebellar nuclei during postnatal development. Given prior evidence implicating HOXA5 in synaptogenesis and early postnatal circuit maturation, we investigated whether its inactivation during this critical developmental window contributes to neurodevelopmental disorder (NDD)-related phenotypes. Using previously generated transcriptomic data, we identified multiple deregulated genes classified as autism spectrum disorder (ASD) risk genes in the SFARI database, several of which are associated with a cerebellar phenotype in mice. We then performed a comprehensive behavioral assessment across motor, social, stereotypical, anxiety-related, and attentional domains in a postnatal inactivation mouse model (Hoxa5-cKO). Motor coordination, learning, gait, and sensorimotor functions were preserved. Social behavior assays yielded no consistent genotype-dependent effects, although results were sensitive to analytical methods and cohort variability. In contrast, Hoxa5-cKO mice exhibited increased stereotypical behaviors, including elevated scratching and marble burying, in the absence of anxiety- or locomotion-related confounds. Importantly, interpretation of social and cognitive phenotypes was impacted by well-known constraints of behavioral neuroscience. We discuss these downfalls and propose additional guidelines. Altogether, our findings indicate that postnatal Hoxa5 deficiency selectively enhances stereotyped behaviors without broadly affecting motor or social functions. The data support a model in which HOXA5 acts as a modulator of postnatal precerebellar circuit connectivity and/or function, with subtle behavioral consequences that require further research in specific genetic or environmental contexts.
Alterations in glutamatergic and GABAergic signaling in ketamine-induced neurotoxicity: mangiferin mitigates neurochemical, oxidative, and astrocytic dysregulation in the rat temporal-frontal cortex.
Anyanwu GE, Chukwu VO, Nto NJ … +2 more , Ojiakor VO, Anyanwu CN
Behav Brain Funct · 2026 Jun · PMID 42366409 · Full text
BACKGROUND: Ketamine is an antagonist of the N-Methyl-D-aspartate (NMDA) receptor with the effect of inducing aberrant excitatory-inhibitory neurotransmission and oxidative neurotoxicity, which mimic the cognitive impair...
BACKGROUND: Ketamine is an antagonist of the N-Methyl-D-aspartate (NMDA) receptor with the effect of inducing aberrant excitatory-inhibitory neurotransmission and oxidative neurotoxicity, which mimic the cognitive impairments found in schizophrenia. This study explored the potential of mangiferin, a strong antioxidant xanthone polyphenol, to normalize neurotransmitter levels and mitigate oxidative and glial changes in rats subjected to ketamine treatment. METHODS: Male Wistar rats were anaesthetised with ketamine (50 mg/kg, i.p., for 7 days) to induce excitotoxicity and subsequently treated for 14 days with mangiferin (25, 50 or 75 mg/kg, p.o.) or risperidone (2 mg/kg, i.p.). Behavioral performance was assessed using the Morris Water Maze, Y-Maze, Open Field, and Novel Object Recognition tests. Neurochemical assays in the prefrontal, hippocampal and temporal cortices measured glutamate, γ-aminobutyric acid (GABA), dopamine, and acetylcholinesterase (AChE) activities. Cellular pathology was evaluated through histopathology (H&E) and immunohistochemistry for glial fibrillary acidic protein (GFAP) and nuclear factor erythroid 2-related factor 2 (Nrf2). RESULTS: Ketamine induced severe cognitive deficits, hyperlocomotion, anxiety-like behavior, reduced cortical GABA and glutamate levels, increased dopamine, and elevated AChE activity-confirming excitatory-inhibitory imbalance and cholinergic disruption. Mangiferin enhanced spatial learning, working memory, recognition memory, and normalized locomotor activity in a dose-dependent manner, with higher doses restoring performance to near control levels. Neurochemically, mangiferin increased GABA and glutamate to baseline levels while decreasing dopamine and AChE hyperactivity. Histology showed preserved cortical cytoarchitecture and reduced neuronal loss and vacuolation. Notably, mangiferin reversed ketamine-induced astrogliosis (decreased GFAP immunoreactivity) and increased nuclear Nrf2 expression, indicating activated endogenous antioxidant defenses. CONCLUSION: Mangiferin exhibited significant neuroprotection against ketamine-induced excitotoxicity through restoration of neurotransmitter homeostasis, establishment of redox resilience, and regulation of astrocytic reactivity. These multifaceted actions underscore its therapeutic potential for neuropsychiatric diseases associated with oxidative stress and glial dysfunction.
Ketamine enhances histone H3 (Ser10) phosphorylation via JNK signaling and multi-omics profiling of the hippocampus in a psychotic-like mouse model.
Zhu XM, Li Y, Liu W … +5 more , Pan Y, Li A, Han GN, Yao J, Wang H
Behav Brain Funct · 2026 Jun · PMID 42351237 · Full text
Ketamine, a dissociative anesthetic, induces behavioral and molecular alterations associated with psychosis-like phenotypes. However, the epigenetic mechanisms bridging its cellular effects with behavioral outcomes are p...
Ketamine, a dissociative anesthetic, induces behavioral and molecular alterations associated with psychosis-like phenotypes. However, the epigenetic mechanisms bridging its cellular effects with behavioral outcomes are poorly defined. Here, we report that ketamine induces histone H3 Ser10 phosphorylation in both hippocampal neurons (HT22 cells) and the mouse hippocampus, an effect primarily driven by JNK activation. Critically, pharmacological inhibition of JNK with SP600125 not only reversed this epigenetic mark but also robustly attenuated ketamine-induced hyperlocomotion and cognitive deficits in mice. Integrated multi-omics analysis of the hippocampus 30 min post-ketamine revealed coordinated transcriptional and chromatin accessibility changes. We identified 262 differentially expressed genes (e.g., MAP3K9) enriched in MAPK signaling and neuroactive ligand-receptor pathways, alongside 165 differentially accessible regions, with motif analysis implicating CTCF as a key regulator. Our findings suggest that JNK-mediated H3S10 phosphorylation may play a critical role in linking ketamine exposure to psychosis-like phenotypes, providing a mechanistic framework that connects stress-sensitive signaling to rapid chromatin remodeling and sustained transcriptional reprogramming. This work unveils potential novel therapeutic targets for psychosis centered on the JNK-H3S10 phosphorylation axis.
Ginkgo biloba extract mitigates behavioral deficits, oxidative stress, and hippocampal remodeling in a rat model of PTSD.
Meamar M, Mohamadi Yarijani Z, Parsaei H … +3 more , Vafaei AA, Rashidy-Pour A, Raise-Abdullahi P
Behav Brain Funct · 2026 Jun · PMID 42332745 · Full text
Post-traumatic stress disorder (PTSD) is associated with cognitive impairments, anxiety, fear extinction deficits, and neurobiological alterations, particularly in the hippocampus. Oxidative stress, reduced brain-derived...
Post-traumatic stress disorder (PTSD) is associated with cognitive impairments, anxiety, fear extinction deficits, and neurobiological alterations, particularly in the hippocampus. Oxidative stress, reduced brain-derived neurotrophic factor (BDNF), and dendritic remodeling are key contributors to these dysfunctions. This study investigated whether Ginkgo biloba extract, known for its antioxidant and neuroprotective properties, could ameliorate PTSD-like symptoms and hippocampal abnormalities in male rats exposed to the single prolonged stress (SPS) model. Adult male Wistar rats were exposed to SPS and treated with Ginkgo biloba extract (20 or 200 mg/kg) for 14 days. Behavioral assessments included anxiety-like behavior, fear extinction, spatial learning and memory, and working memory. Hippocampal tissue was analyzed for oxidative stress markers (MDA, SOD, TAC), BDNF expression (Western blot), and CA3 dendritic morphology (Golgi-Cox impregnation method). SPS exposure induced marked behavioral deficits, elevated oxidative stress, reduced BDNF expression, and dendritic atrophy in CA3 pyramidal neurons. Ginkgo biloba extract, particularly at a dose of 200 mg/kg, significantly attenuated anxiety-like behaviors, facilitated fear extinction, improved memory performance, reduced oxidative damage, restored BDNF levels, and reversed dendritic retraction and branching deficits in the CA3 region of the hippocampus. These findings demonstrate that Ginkgo biloba extract exerts neuroprotective effects against trauma-induced behavioral, molecular, and structural abnormalities in a validated animal model of PTSD. While promising, these results are based on preclinical data, and further studies are necessary to determine whether similar benefits can be translated to clinical populations.
Rich-club organization and functional brain network metrics during facial emotional processing: a task-based fMRI study.
Gholam Tamimi M, Daliri MR
Behav Brain Funct · 2026 Jun · PMID 42304477 · Full text
BACKGROUND: Emotion is a complex psychological phenomenon involving both arousal and valence. emotional processing (EP) refers to the ability to perceive and interpret emotional stimuli, such as facial expressions or voc...
BACKGROUND: Emotion is a complex psychological phenomenon involving both arousal and valence. emotional processing (EP) refers to the ability to perceive and interpret emotional stimuli, such as facial expressions or vocal cues. METHODS: In this study, we investigated functional connectivity (FC), graph-theoretical network measures, and rich-club organization during EP using task-based functional magnetic resonance imaging (fMRI) data from 100 healthy participants from the Human Connectome Project (HCP). Mean time series were extracted from 264 regions of interest (ROIs) defined by the Power Atlas, encompassing 10 large-scale functional networks. Pairwise Pearson correlation coefficients were computed to generate FC matrices, which were then thresholded using the orthogonal minimal spanning tree (OMST) method to form adjacency matrices. These matrices served as the basis for calculating global and local network metrics and analyzing rich-club organization. Permutation-based paired t-tests (p < 0.05, 1000 permutations) and family wise error (FWE)-corrected were used to identify significant differences between face and shape conditions. RESULTS: Our findings indicate a significant modulation of neural activity between the face and shape conditions during facial EP. Significant differences in FC, network metrics, and rich-club organization were observed at both ROI and network levels. High-level cognitive networks exhibited stronger positive correlations, whereas low-level perceptual networks showed increased anticorrelations. Global network measures, including modularity, mean local efficiency, and clustering coefficient, were increased, indicating enhanced functional segregation. Simultaneously, selective rich-club connectivity among hubs in dorsal attention, frontoparietal, visual, somatomotor, and subcortical networks suggests preserved network integration at the mesoscale level. These findings uniquely combine rich-club organization with graph-theoretical measures across 10 large-scale networks, providing novel insights into hub coordination under emotional demands. CONCLUSIONS: EP induces reorganization of brain networks, enhancing functional specialization while selectively modulating hub regions to maintain efficient integration. These results offer deeper insight into neural mechanisms underlying emotional cognition and may help explain connectivity alterations in emotional and affective disorders.
Postpartum enhancement of spatial learning and cognitive flexibility: an IntelliCage study.
Cservenák M, Darai L, Kállai TC … +5 more , Záhonyi B, Lukács A, Bencsik N, Détári L, Dobolyi A
Behav Brain Funct · 2026 Jun · PMID 42286596 · Full text
The transition to motherhood has been shown to result in significant changes in the structure and function of the brain, with particular emphasis on the enhancement of cognitive abilities that are essential for survival....
The transition to motherhood has been shown to result in significant changes in the structure and function of the brain, with particular emphasis on the enhancement of cognitive abilities that are essential for survival. Specifically, in murine models, spatial learning and cognitive flexibility have been identified as critical components of mothering. While cognitive enhancements during the postpartum period have been observed in various experimental setups, research using long-term data collection with automated monitoring in a home cage setup is lacking despite its reliability compared to other experimental procedures. This study aims to address this knowledge gap by systematically examining spatial learning and cognitive flexibility in female mice during the reproductive stages using the IntelliCage system. The results showed that female mice in the postpartum phase outperformed pregnant and nulliparous females in place learning, reversal learning, and fixed schedule drinking tasks, demonstrating faster adaptation and superior retention of information. Postpartum mothers showed elevated cognitive ability in spatial learning, and also showed increased flexibility compared to the control/pregnant group suggesting a greater ability to update previously learned associations. The identification of these improvements in maternal behavior may provide novel insights into how reproductive experiences impact brain function, with implications for maternal health and broader cognitive research.
Developmental trajectories of prefrontal activation underlying emotional inhibitory control from adolescence to young adulthood: a functional near-infrared spectroscopy study.
Chen T, Jiang L, Wen R … +1 more , Jiang C
Behav Brain Funct · 2026 Jun · PMID 42277909 · Full text
BACKGROUND: Understanding the neural maturation of emotional inhibitory control (IC) from adolescence to young adulthood is critical but remains incompletely characterized. The present study examined age-related differen...
BACKGROUND: Understanding the neural maturation of emotional inhibitory control (IC) from adolescence to young adulthood is critical but remains incompletely characterized. The present study examined age-related differences in prefrontal activation during emotional conflict processing using functional near-infrared spectroscopy (fNIRS). METHODS: Twenty-six adolescents (ages 13-16, 15 male) and thirty young adults (ages 18-22, 16 male) completed an emotional Flanker task while behavioral responses and prefrontal hemodynamic activity were recorded with fNIRS. RESULTS: Both groups exhibited a significant emotional Flanker effect, with slower responses on incongruent than congruent trials. fNIRS results suggested age-related differences in prefrontal recruitment patterns. Adolescents showed relatively stronger OHb changes in the right dorsolateral prefrontal cortex (DLPFC), indicating a more right-lateralized response to emotional conflict. In contrast, young adults exhibited a more bilateral pattern of DLPFC activation. CONCLUSIONS: These findings suggest a developmental shift from relatively focal, right-lateralized prefrontal engagement in adolescence to more distributed bilateral recruitment in young adulthood. Such age-related differences may reflect changes in cognitive strategies alongside ongoing maturation of prefrontal networks, with localized right-sided activation in adolescents supporting behavioral performance through compensatory engagement and bilateral recruitment in young adults reflecting greater network integration and neural efficiency.
Astrocyte-derived IL-17A facilitates angiogenesis following ischemia-like injury via an IL-6-dependent STAT3-VEGF signaling cascade.
Chen X, Zhang Y, Huang T … +5 more , Peng J, Zeng Y, Zhao Y, Jiang H, Liu L
Behav Brain Funct · 2026 Jun · PMID 42260524 · Full text
BACKGROUND: Angiogenesis plays a vital role in cerebral tissue repair following ischemic stroke. Prior in vivo studies have identified astrocytic interleukin-17A (IL-17A) as a critical mediator of post-ischemic angiogene...
BACKGROUND: Angiogenesis plays a vital role in cerebral tissue repair following ischemic stroke. Prior in vivo studies have identified astrocytic interleukin-17A (IL-17A) as a critical mediator of post-ischemic angiogenesis, associated with upregulation of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). However, the intracellular signaling mechanisms underlying these effects within astrocytes have not been fully elucidated. This study delineates a specific intracellular signaling mechanism through which astrocytic IL-17A promotes angiogenesis following an in vitro ischemia-like injury. METHODS: Primary astrocytes were exposed to oxygen-glucose deprivation followed by reperfusion (OGD/R). Astrocyte viability was assessed using the Cell Counting Kit-8 assay. Brain microvascular endothelial cells (BMECs) were cultured with astrocyte-conditioned medium (ACM). Astrocytes were treated with recombinant IL-17A (rIL-17A), IL-17A-targeted small interfering RNA, a neutralizing antibody against IL-6, or the Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway inhibitor AG490. Protein levels were quantified, and angiogenic capacity was determined via tube formation assays and CD34 expression analysis. RESULTS: Exposure to OGD/R increased IL-17A secretion from astrocytes. Treatment with rIL-17A enhanced astrocyte viability and induced IL-6 production. Activation of the JAK2/STAT3 pathway by IL-6 was required for the subsequent VEGF upregulation. Consequently, ACM from rIL-17A-treated astrocytes significantly promoted angiogenic activity in BMECs, as evidenced by enhanced tube formation. These pro-angiogenic effects were significantly attenuated by IL-17A knockdown, IL-6 neutralization, or inhibition of JAK2/STAT3 signaling in astrocytes. CONCLUSIONS: This study delineates a specific intracellular signaling mechanism through which astrocytic IL-17A promotes angiogenesis following ischemia-like injury. The findings identify an IL-6-dependent activation of the STAT3-VEGF signaling axis as a key mediator of this process, underscoring the therapeutic potential of targeting astrocytic IL-17A signaling in post-stroke angiogenic repair.
A narrative review of behavioral tests across mammalian models in neuroscience.
Huang H, Li H
Behav Brain Funct · 2026 Jun · PMID 42251419 · Full text
Mammalian models are widely employed in the research of human diseases. Behavioral tests in animals is a critical evaluative approach in scientific research, offering insights into complex disease pathophysiology and fac...
Mammalian models are widely employed in the research of human diseases. Behavioral tests in animals is a critical evaluative approach in scientific research, offering insights into complex disease pathophysiology and facilitating the assessment of novel therapeutic interventions. Currently, behavioral testing paradigms are extensively applied in mammalian research, particularly in rodent models. Compared to rodents, the brains of large mammals exhibit closer anatomical and biochemical homology to the human brain, thereby endowing them with significant value in neuroscience. Numerous neurological disorders have been successfully used large mammals as models, with the widespread application of behavioral testing methods for these species. This review summarizes established behavioral testing methodologies developed for both small and large mammalian species, and discusses their applications, efficacy, and limitations.
Knockout in zebrafish suggests a role of BDNF in behavioural and cognitive plasticity.
Rovegno E, Gatto E, Frigato E … +2 more , Bertolucci C, Lucon-Xiccato T
Behav Brain Funct · 2026 May · PMID 42178558 · Full text
An adaptive mechanism observed in virtually all living animals is the phenotypic plasticity, a phenomenon by which different phenotypes can develop from the same genotype depending on the environment experienced. Phenoty...
An adaptive mechanism observed in virtually all living animals is the phenotypic plasticity, a phenomenon by which different phenotypes can develop from the same genotype depending on the environment experienced. Phenotypic plasticity can involve a range of life-history, physiology, morphology, and also behavioural and cognitive traits. For example, individuals exposed to complex and enriched environments generally show greater learning abilities compared to individuals raised in simpler or barren environments. Several studies suggest that brain-derived neurotrophic factor (BDNF) may be involved in this plasticity, as it is often differentially expressed in individuals exposed to different environments. We investigated this possibility in fish, taking advantage of a knockout zebrafish line lacking the gene coding for BDNF (bdnf). Zebrafish from both the knockout (bdnf ) and control (bdnf ) lines were raised in either barren or enriched environments, and their behavioural and cognitive phenotypes were analysed. bdnf zebrafish exhibited higher behavioural and cognitive plasticity compared to bdnf controls, as evidenced by a pronounced increase in activity and learning scores following exposure to environmental enrichment. These results suggest that BDNF may play a modulatory role in phenotypic plasticity, although broader organisational alterations resulting from the absence of BDNF during development in knockout zebrafish cannot be ruled out. An additional exploratory analysis of the expression of other neuroplasticity-related genes identified potential pathways that may be involved in this effect.
Ventromedial hypothalamus IL-6 signaling mediates the excessive aggressive behavior induced by late-gestational sleep deprivation in male mice.
Zhou F, Yu X, Gong M … +7 more , Liu X, Li X, Li Y, Song L, Wang S, Guo Q, Shi H
Behav Brain Funct · 2026 May · PMID 42121275 · Full text
BACKGROUND: Aggressive behavior is an evolutionarily conserved trait that supports resource acquisition and survival; however, excessive or dysregulated aggression is closely associated with neuropsychiatric disorders an...
BACKGROUND: Aggressive behavior is an evolutionarily conserved trait that supports resource acquisition and survival; however, excessive or dysregulated aggression is closely associated with neuropsychiatric disorders and social dysfunction. Maternal sleep deprivation (SD) during late gestation is a common yet underexplored environmental stressor that may disrupt offspring neurodevelopment through immune-mediated pathways. The present study investigated whether SD during late pregnancy alters aggressive behavior in offspring during early adulthood, explored the underlying neuroimmune mechanisms, and evaluated the potential of a post-weaning ketogenic diet (KD) as a non-pharmacological intervention. RESULTS: Behavioral analyses revealed that late-gestational SD significantly increased both defensive and proactive aggressive behaviors in offspring mice during early adulthood. Peripheral immune assessment revealed that serum IL-6 levels were elevated in male offspring, while no significant change was observed in females. Pharmacological experiments demonstrated a causal role of IL-6 in aggression regulation, as peripheral administration of IL-6 increased aggression in control male offspring mice, whereas administration of anti-IL-6 in sleep deprivation-exposed male offspring normalized aggressive behavior. Neurobiological analyses identified enhanced neuronal activation, increased IL-6 and IL-6R expression, and pronounced microglial activation in the ventromedial hypothalamus (VMH). Consistently, VMH administration of IL-6 increased aggressive behavior, while injection of anti-IL-6 antibody attenuated the heightened aggression in SD-exposed male offspring mice. Chemogenetic inhibition of VMH neurons effectively attenuated the heightened aggression, indicating a critical role for this neural circuit. Importantly, post-weaning KD suppressed microglial overactivation and reduced IL-6 signaling in the VMH, restored neuroimmune homeostasis, and reversed abnormal aggressive behaviors. CONCLUSIONS: These findings demonstrate that late-gestational maternal SD promotes excessive aggression in male offspring mice through IL-6-mediated neuroimmune dysregulation within the VMH. Moreover, post-weaning KD intervention effectively rescues both immune imbalance and behavioral abnormalities. This study highlights the long-term behavioral consequences of prenatal sleep loss and identifies dietary modulation of neuroimmune pathways as a promising non-pharmacological strategy for mitigating pathological aggression induced by early-life stress.
Domain-general behavioral gains and neural correlates of cognitive training in healthy populations: a neuroimaging meta-analysis.
Li G, Liu C, Liu Y … +1 more , Zhang Y
Behav Brain Funct · 2026 May · PMID 42092905 · Full text
Preventive strategies to promote cognitive health are increasingly prioritized, yet the extent to which cognitive training yields domain-general behavioral gains and neural correlates remains unclear. Here we conducted a...
Preventive strategies to promote cognitive health are increasingly prioritized, yet the extent to which cognitive training yields domain-general behavioral gains and neural correlates remains unclear. Here we conducted a systematic review and meta-analysis of 67 neuroimaging studies to quantify the domain-general effects of cognitive training on cognitive performance and task-related activation changes, and to test associations between behavioral gains and neural adaptations. Across training domains, task paradigms and age groups, cognitive training significantly improved cognitive task performance (Hedges' g = 0.546, 95% CI = 0.414-0.678; t = 8.149; p < 0.0001), accompanied by increased activation in the right superior parietal lobule (R.SPL) and decreased activation in the bilateral anterior cingulate cortex (ACC). Regression analyses further indicated that cognitive improvements were closely associated with these activation changes, with training completion rate emerging as a key moderator. Collectively, these findings identify candidate domain-general neural signatures of cognitive training-induced plasticity and provide an initial empirical basis for the evidence-informed design and optimization of cognitive training interventions.
Neuropeptide S modulation of learning and memory: a systematic review.
Caragea VM, Jüngling K, Méndez-Couz M
Behav Brain Funct · 2026 May · PMID 42069596 · Full text
BACKGROUND: In the last two decades, Neuropeptide S (NPS) has been identified as a key bioactive peptide in the mammalian brain, influencing fear, anxiety, wakefulness, reward, and learning. While some reviews have addre...
BACKGROUND: In the last two decades, Neuropeptide S (NPS) has been identified as a key bioactive peptide in the mammalian brain, influencing fear, anxiety, wakefulness, reward, and learning. While some reviews have addressed its role in reward-seeking and anxiety, few have addressed its particular role in learning and memory. The neuropeptide S receptor 1 is highly expressed in key areas for learning processing, such as the hippocampus, cortex, thalamus, and amygdala. This review aims to examine evidence from human and animal studies that focused on the NPS system's role in modulating learning and memory. A special focus is given to experiments addressing the impact of NPS on associative learning leading to addiction and in fear conditioning, pointing to its potential therapeutic value in associated pathologies. MAIN BODY: An advanced search was conducted using the databases PubMed, Google Scholar, Web of Science, and Scopus, focusing on memory and Neuropeptide S. The reviewed data suggest that NPS modulation occurs at all memory phases, including acquisition, consolidation, and retrieval, and in extinction learning, whether motivated by appetitive or aversive stimuli. The summarized evidence shows that the NPS system interferes with working and short-term memory, mitigates learning impairments, enhances spatial and object memory consolidation, supports fear extinction learning and inhibitory avoidance consolidation, and reinstates drug-seeking behaviors. The NPS system closely interacts with key neuromodulators, including orexinergic, dopaminergic, and noradrenergic systems, in influencing memory. CONCLUSION: The Neuropeptide S system emerges as a critical modulator of memory processes. The NPS signaling may preferentially influence learning that involves emotionally or motivationally relevant stimuli. This highlights the NPS system's potential as a target for therapeutic interventions for particular memory impairments.
Low-level laser therapy enhances neuroprotection and functional recovery after neonatal hypoxic-ischemic injury via potential activation of Nrf2/HO-1 and Akt pathways.
Liu P, Zhang S, Wang H … +1 more , Li Z
Behav Brain Funct · 2026 Apr · PMID 42050654 · Full text
BACKGROUND: Neonatal hypoxic–ischemic encephalopathy (HIE) is a leading cause of neurodevelopmental disability. Low-level laser therapy (LLLT), or photobiomodulation, has shown neuroprotective potential, but its long-ter...
BACKGROUND: Neonatal hypoxic–ischemic encephalopathy (HIE) is a leading cause of neurodevelopmental disability. Low-level laser therapy (LLLT), or photobiomodulation, has shown neuroprotective potential, but its long-term effects and region-specific responses remain poorly defined. METHODS: Neonatal rats subjected to hypoxic–ischemic brain damage (HIBD) received transcranial 810-nm LLLT (24 mW/cm², 10 min/session, twice daily for three days). Histological, immunofluorescence, and Western blot analyses assessed neuronal integrity, glial activation, and signaling pathway changes. Sensorimotor function was evaluated by grip traction and open-field tests, and spatial learning and memory were assessed using the Morris water maze (MWM) at long-term follow-up. RESULTS: LLLT reduced neuronal loss and glial reactivity and was associated with increased Nrf2/HO-1 and Akt signaling at early time points. Behaviorally, LLLT improved motor and cognitive performance, with benefits persisting up to 20 weeks post-injury. CONCLUSION: Early LLLT is associated with sustained functional recovery after neonatal hypoxic–ischemic injury. These effects may involve early modulation of antioxidant and pro-survival signaling pathways, although the mechanisms underlying long-term outcomes require further investigation.
Adverse childhood experiences, depressive symptoms, and non-suicidal self-injury in Chinese adolescents: the moderating role of SKA2 gene rs7208505 polymorphism.
Wang Y, Liang Q, Zhou W … +7 more , Wang Y, Tian S, Hu X, Tian J, Liu Y, Fang H, Wang W
Behav Brain Funct · 2026 Apr · PMID 42010618 · Full text
BACKGROUND: The Hypothalamic-pituitary-adrenal axis (HPA) and its single nucleotide polymorphisms (SNPs) potentially influence depressive symptoms and non-suicidal self-injury (NSSI) among adolescents. Adverse childhood...
BACKGROUND: The Hypothalamic-pituitary-adrenal axis (HPA) and its single nucleotide polymorphisms (SNPs) potentially influence depressive symptoms and non-suicidal self-injury (NSSI) among adolescents. Adverse childhood experiences (ACEs) may dysregulate HPA axis functioning, with these complex gene-environment interactions showing significant heterogeneity across individuals. This study examined whether depressive symptoms mediate the relationship between ACEs and adolescent NSSI, and whether HPA axis genetic polymorphisms moderate this indirect pathway. METHODS: For this study, 172 adolescents aged 12 to 18 years were recruited from Xuzhou Oriental Hospital affiliated with Xuzhou Medical University as the NSSI group. Additionally, 58 age-, sex-, residence-, and health-matched volunteers were recruited from the local area as the healthy control group. Demographic information was collected through questionnaires, and adverse childhood experiences, depressive symptoms, and non-suicidal self-injury behaviors were assessed using the Adverse Childhood Experiences Scale (ACEs Scale), the Beck Depression Inventory-II (BDI-II), and the Non-Suicidal Self-Injury Behavior Scale (NSSI-BS). Blood samples were collected for HPA axis genotyping targeting the following loci: SKA2 (rs7208505, rs9911583), SLC1A3 (rs2269272), FKBP5 (rs9470080), and AVPR1B (rs28373064), which were analyzed using TaqMan-PCR. All statistical analyses were performed in SPSS 27.0, including Hardy-Weinberg equilibrium (HWE), χ² test, and Pearson’s correlation coefficient, as well as PROCESS macro-model mediation analysis and simple slope analysis. RESULTS: Depressive symptoms were found to mediate the association between ACEs and NSSI. The SKA2-rs7208505 polymorphism significantly moderated the relationship between ACEs and depressive symptoms, influencing the indirect pathway from ACEs to depressive symptoms to NSSI. Adolescents with the AA genotype of the SKA2-rs7208505 polymorphism were more susceptible to ACEs and more likely to develop depressive symptoms compared to those with GA and GG genotypes. CONCLUSION: Timely identification and interventions targeting depressive symptoms, especially among individuals with AA genotypes of SKA2-rs7208505 who have experienced ACEs, may be crucial for preventing or reducing the risk of NSSI in adolescents.
How time pressure disrupts inhibitory control: neural dissociations between interference and response inhibition.
Ding Z, Wu W, Tian Y
Behav Brain Funct · 2026 Apr · PMID 41992340 · Full text
BACKGROUND: In modern fast-paced societies, subjective time pressure has become a common psychological stressor that may impair inhibitory control, a core component of executive function. Inhibitory control consists of t...
BACKGROUND: In modern fast-paced societies, subjective time pressure has become a common psychological stressor that may impair inhibitory control, a core component of executive function. Inhibitory control consists of two subprocesses—interference control and response inhibition—yet how time pressure differentially affects these processes and their neural mechanisms remains insufficiently understood. METHODS: This study manipulated subjective time pressure and employed the Flanker task (interference control) and the Go/NoGo task (response inhibition) to examine behavioral performance, event-related potentials (ERPs), and time–frequency oscillations. Forty healthy adults completed both time-pressure and no time pressure conditions. ERP analyses focused on the P1, N1, P2, N2, and P3 components, while time–frequency analyses were performed both across the full frequency range (3–30 Hz) and within specific frequency bands (θ and β), using cluster-based permutation tests. RESULTS: Behaviorally, time pressure reduced accuracy, especially in incongruent Flanker trials and NoGo trials, while accelerating overall reaction times. ERP results showed enhanced N2 and P3 amplitudes in the Flanker task. In the Go/NoGo task, time pressure led to reduced P2, but increased N2 and P3. Time–frequency analysis revealed higher theta power during early control and increased beta power during later inhibition under time pressure. CONCLUSION: Taken together, the behavioral, ERP, and oscillatory findings suggest that subjective time pressure is associated with alterations in inhibitory control, with distinct patterns observed for interference control and response inhibition. Specifically, interference control under time pressure was characterized by enhanced late-stage neural activity without corresponding oscillatory changes, whereas response inhibition was accompanied by modulations in both early and late neural processes, involving enhanced N2 and P3 components as well as increased θ and β band activity. These findings suggest that time pressure may affect interference control and response inhibition through partially distinct neurocognitive mechanisms, rather than a single unified pathway.
Neural compensation through dorsal stream involvement in visual word recognition under perceptual degradation in a transparent language: evidence from fMRI.
Giubergia A, Lampis V, Mauri C … +5 more , Montano F, Ferrazzi G, Castellaro M, Bertoldo A, Peruzzo D
Behav Brain Funct · 2026 Apr · PMID 41923120 · Full text
BACKGROUND: Visual word recognition relies on a finely tuned interplay between the ventral and dorsal visual pathways. While the ventral stream is classically regarded as the primary substrate for orthographic processing...
BACKGROUND: Visual word recognition relies on a finely tuned interplay between the ventral and dorsal visual pathways. While the ventral stream is classically regarded as the primary substrate for orthographic processing, converging evidence suggests that the dorsal stream may provide compensatory support under increased perceptual demands. In particular, the degree of orthographic transparency influences the relative involvement of these pathways. We conducted a functional MRI study in Italian, a transparent orthography, to investigate supportive neural recruitment during reading under perceptual degradation. Participants performed a word recognition task in which visual real words were degraded through four types of visual manipulation (rotation, mirroring, reduced contrast, increased letter spacing) to increase processing difficulty. Both whole-brain and region-of-interest analyses were performed. RESULTS: Analyses revealed robust engagement of canonical ventral reading regions across conditions, alongside increased recruitment of dorsal stream areas during degraded word processing, and this dorsal involvement scaled with increasing level of visual degradation. This dorsal involvement was most prominent in the superior parietal and temporo-parietal cortices, consistent with their role in visuo-spatial attention CONCLUSION: These findings suggest that, even in transparent languages where phonological decoding is relatively straightforward, the dorsal pathway can be part of a flexible reorganisation of the reading system. By demonstrating stimulus-driven adaptation of the reading network, our results provide novel insights into the neural flexibility underlying visual word recognition and highlight the importance of dorsal-ventral interactions in sustaining reading performance under suboptimal perceptual conditions.
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