Behavioral and Brain Functions最新文献

{"title":"Differential neuronal functions of LNX1 and LNX2 revealed by behavioural analysis in single and double knockout mice.","authors":"Laura Cioccarelli, Joan A Lenihan, Leah G Erwin, Paul W Young","doi":"10.1186/s12993-025-00276-z","DOIUrl":"https://doi.org/10.1186/s12993-025-00276-z","url":null,"abstract":"<p><strong>Background: </strong>Ligand of NUMB protein-X 1 (LNX1) and LNX2 proteins are closely related PDZ domain-containing E3 ubiquitin ligases that interact with and potentially modulate numerous synaptic and neurodevelopmentally important proteins. While both LNX1 and LNX2 are expressed in neurons, it is noteworthy that neuronal LNX1 isoforms lack the catalytic domain responsible for ubiquitination of substrates. Thus, the shared interaction partners of LNX1 and LNX2 might be differentially regulated by these proteins, with LNX1 acting as a stabilizing scaffold while LNX2 may promote their ubiquitination and degradation. Despite the identification of many LNX interacting proteins and substrates, our understanding of the distinct in vivo functions of LNX1 and LNX2 remains very incomplete.</p><p><strong>Results: </strong>We previously reported that mice lacking both LNX1 in the central nervous system and LNX2 globally exhibit decreased anxiety-related behaviour. Here we significantly extend this work by examining anxiety-related and risk-taking behaviours in Lnx1^-/- and Lnx2^-/- single knockout animals for the first time and by analysing previously unexplored aspects of behaviour in both single and double knockout animals. While the absence of both LNX1 and LNX2 contributes to the decreased anxiety-related behaviour of double knockout animals in the open field and elevated plus maze tests, the elimination of LNX2 plays a more prominent role in altered behaviour in the dark-light emergence test and wire beam bridge risk-taking paradigms. By contrast, Lnx knockout mice of all genotypes were indistinguishable from wildtype animals in the marble burying, stress-induced hyperthermia and novel object recognition tests. Analysis of the ultrasonic vocalizations of pups following maternal separation revealed significant differences in call properties and vocal repertoire for Lnx1^-/- and Lnx1^-/-;Lnx2^-/- double knockout animals. Finally, decreased body weight previously noted in double knockout animals could be attributed largely to Lnx1 gene knockout.</p><p><strong>Conclusions: </strong>These results identify specific roles of LNX1 and LNX2 proteins in modulating distinct aspects of anxiety and risk-taking behaviour and social communication in mice. They also reveal an unexpected role for neuronally expressed LNX1 isoforms in determining body weight. These novel insights into the differential neuronal functions of LNX1 and LNX2 proteins provide a foundation for mechanistic studies of these phenomena.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"13"},"PeriodicalIF":4.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging-validated correlates and implications of the pathophysiologic mechanisms of ageing-related cerebral large artery and small vessel diseases: a systematic review and meta-analysis.","authors":"Joseph A Ackah, Xuelong Li, Huixing Zeng, Xiangyan Chen","doi":"10.1186/s12993-025-00274-1","DOIUrl":"https://doi.org/10.1186/s12993-025-00274-1","url":null,"abstract":"<p><strong>Background: </strong>Cerebral large artery and small vessel diseases are considered substrates of neurological disorders. We explored how the mechanisms of neurovascular uncoupling, dysfunctional blood-brain-barrier (BBB), compromised glymphatic pathway, and impaired cerebrovascular reactivity (CVR) and autoregulation, identified through diverse neuroimaging techniques, impact cerebral large artery and small vessel diseases.</p><p><strong>Methods: </strong>Studies (1990-2024) that reported on neuroradiological findings on ageing-related cerebral large artery and small vessel diseases were reviewed. Fifty-two studies involving 23,693 participants explored the disease mechanisms, 9 studies (sample size = 3,729) of which compared metrics of cerebrovascular functions (CF) between participants with cerebral large artery and small vessel diseases (target group) and controls with no vascular disease. Measures of CF included CVR, cerebral blood flow (CBF), blood pressure and arterial stiffness.</p><p><strong>Results: </strong>The findings from 9 studies (sample size = 3,729, mean age = 60.2 ± 11.5 years), revealed negative effect sizes of CVR [SMD = - 1.86 (95% CI - 2.80, - 0.92)] and CBF [SMD = - 2.26 (95% CI - 4.16, - 0.35)], respectively indicating a reduction in cerebrovascular functions in the target group compared to their controls. Conversely, there were significant increases in the measures of blood pressure [SMD = 0.32 (95% CI 0.18, 0.46)] and arterial stiffness [SMD = 0.87 (95% CI 0.77, 0.98)], which signified poor cerebrovascular functions in the target group. In the combined model the overall average effect size was negative [SMD = - 0.81 (95% CI - 1.53 to - 0.08), p < 0.001]. Comparatively, this suggests that the negative impacts of CVR and CBF reductions significantly outweighed the effects of blood pressure and arterial stiffness, thereby predominantly shaping the overall model. Against their controls, trends of reduction in CF were observed exclusively among participants with cerebral large artery disease (SMD = - 2.09 [95% CI: - 3.57, - 0.62]), as well as those with small vessel diseases (SMD = - 0.85 [95% CI - 1.34, - 0.36]). We further delineated the underlying mechanisms and discussed their interconnectedness with cognitive impairments.</p><p><strong>Conclusion: </strong>In a vicious cycle, dysfunctional mechanisms in the glymphatic system, neurovascular unit, BBB, autoregulation, and reactivity play distinct roles that contribute to reduced CF and cognitive risk among individuals with cerebral large artery and/or small vessel diseases. Reduction in CVR and CBF points to reductions in CF, which is associated with increased risk of cognitive impairment among ageing populations ≥ 60 years.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"12"},"PeriodicalIF":4.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute high-intensity noise exposure exacerbates anxiety-like behavior via neuroinflammation and blood brain barrier disruption of hippocampus in male rats.","authors":"Yifei Song, Haoyu Zhang, Xiaoni Wang, Lei Huang, Yiting Kang, Zeguo Feng, Fadong Zhao, Hongwei Zhuang, Jianbao Zhang","doi":"10.1186/s12993-025-00275-0","DOIUrl":"https://doi.org/10.1186/s12993-025-00275-0","url":null,"abstract":"<p><p>The health risks associated with acute noise exposure are increasing, particularly the risk of mental health. This study aims to identify the association between acute high-intensity noise exposure and anxiety behavior in male rats, and to explore the associated neurobiological mechanisms. Male rats were subjected to different levels of acute high-intensity noise to determine the intensity that causes long-lasting anxiety-like behaviors. Anxiety-like behaviors were evaluated using the open field test (OFT) and the elevated plus maze test (EPMT) on the third day and 1month post-exposure, respectively. A range of techniques, including immunofluorescence staining, western blot, ELISA, and real-time quantitative PCR, were used to investigate neuronal apoptosis, glial cell activation, neuroinflammation, and blood-brain barrier (BBB) disruption in the hippocampus. Upon exposure to 135 dB of acute noise, male rats exhibited enduring anxiety-like behaviors. Subsequent investigations discovered that this noise intensity not only activated glial cells and triggered neuroinflammation within the hippocampus but also decreased the expression levels of ZO-1, claudin-5, and occludin, suggesting a disruption of the BBB. Additionally, this exposure was associated with the induction of neuronal apoptosis in the hippocampal region. In conclusion, acute exposure to 135 dB noise may cause persistent anxiety in male rats through a cyclical interaction between neuroinflammation and BBB disruption, potentially leading to neuronal apoptosis.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"11"},"PeriodicalIF":4.7,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive review on the impact of polyphenol supplementation and exercise on depression and brain function parameters.","authors":"Shihong Jie, Aili Fu, Chuan Wang, Sogand Rajabi","doi":"10.1186/s12993-025-00273-2","DOIUrl":"10.1186/s12993-025-00273-2","url":null,"abstract":"<p><p>The objective of this review study is to examine the combined antidepressant effects of exercise and polyphenol supplementation, with a focus on specific polyphenolic compounds such as crocin, curcumin, and quercetin, as well as different forms of physical exercise, including aerobic and resistance training. The research examines how these interventions influence depressive-like behaviors, cognitive function, and neurochemical markers in animal models and human participants. The findings demonstrate that both exercise and polyphenols independently contribute to mood enhancement, reduced anxiety, and improved cognitive function through mechanisms such as neurogenesis, neurotransmitter modulation, and anti-inflammatory effects. Notably, the combined interventions showed a synergistic effect, providing more significant benefits in reducing symptoms of depression and anxiety, enhancing cognitive performance, and supporting overall mental well-being. These results suggest that integrating exercise and polyphenol supplementation could be a promising non-pharmacological approach to managing depression and related disorders.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"10"},"PeriodicalIF":4.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of cerebellar-cortical connectivity in modulating attentional abilities: insight from football athletes.","authors":"Jian Wang, Siyu Gao, Junfu Tian, Hao Hong, Chenglin Zhou","doi":"10.1186/s12993-025-00272-3","DOIUrl":"10.1186/s12993-025-00272-3","url":null,"abstract":"<p><p>Neuroplasticity, a phenomenon present throughout the lifespan, is thought to be influenced by physical training. However, the relationship between neuroplastic differences and attentional abilities remains unclear. This study explored the differences in brain function and attentional abilities between professional football athletes and novices, and further investigated the relationship between the two. To address this question, we included 49 football athletes and 63 novices in our study, collecting data on resting-state functional connectivity and Attention Network Test (ANT). Behavioral results from the ANT indicated that football experts had superior orienting attention but weaker alerting functions compared to novices, with no difference in executive control attention. fMRI results revealed that football experts exhibited higher fractional Amplitude of Low-Frequency Fluctuations (fALFF) values in the bilateral anterior cerebellar lobes, bilateral insula, and left superior temporal gyrus. Functional connectivity analysis showed increased connectivity between the left anterior cerebellar lobe and various cortical regions, including the right supramarginal gyrus, left precuneus, left superior frontal gyrus, bilateral posterior cerebellar lobes, and bilateral precentral gyri in experts compared to novices. More importantly, in the expert group but not in novice group, functional connectivity differences significantly predicted attentional orienting scores. Graph theoretical analysis showed that experts exhibited higher betweenness centrality and node efficiency in the right cerebellar lobule III (Cerebelum_3_R) node. Our findings demonstrate that long-term professional football training may significantly affect neuroplasticity and attentional functions. Importantly, our analysis reveals a substantive connection between these two aspects, suggesting that the integration of neuroplastic and attentional changes is likely mediated by cerebellar-cortical connectivity.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"9"},"PeriodicalIF":4.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neonatal maternal separation causes depressive-like behavior and potentiates memory impairment induced by amyloid-β oligomers in adult mice.","authors":"Patrick R Suman, Grasielle C Kincheski, Rudimar L Frozza, Fernanda G De Felice, Sergio T Ferreira","doi":"10.1186/s12993-025-00266-1","DOIUrl":"10.1186/s12993-025-00266-1","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is characterized by memory decline and mood alterations. A growing body of evidence implicates stress and other social determinants of health as potential contributors to the progressive cerebral alterations that culminate in AD. In the current study, we investigated the impact of neonatal maternal separation (MS) on the susceptibility of male and female mice to AD-associated memory impairments and depressive-like behavior in adulthood, and on brain levels of pro-inflammatory cytokines and neurotransmitters.</p><p><strong>Methodology: </strong>Male and female Swiss mice were exposed to MS for 180 min daily from post-natal day 1 to 10. Seventy days post-MS, mice received an intracerebroventricular infusion of amyloid-β oligomers (AβOs), and memory and mood were evaluated. Levels of TNF-α, IL-1β, serotonin, dopamine, and related metabolites were determined in the cortex and hippocampus.</p><p><strong>Results: </strong>Previous exposure to MS alone did not cause memory impairments in adult mice. Interestingly, however, MS increased the susceptibility of adult male mice to memory impairment and depressive-like behavior induced by AβOs, and potentiated the inhibitory impact of AβOs on memory in adult females. Females were more susceptible to depressive-like behavior caused by a low dose of AβOs, regardless of MS. No changes in IL-1β were found. A decrease in TNF-α was selectively found in females exposed to MS that received an infusion of 1 pmol AβOs. MS led to an increase in serotonin (5-HT) in the hippocampus of male mice, without influencing the levels of the serotonin metabolite, 5-HIAA. Changes in serotonin turnover were predominantly observed in the cortex of female mice. No changes in dopamine or its metabolites were induced by MS or AβOs in male or female mice.</p><p><strong>Conclusions: </strong>Neonatal MS enhances the susceptibility of adult mice to AD-associated cognitive deficits and depressive-like behavior in a sex-specific manner. This suggests that early life stress may play a role in the development of AD.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"8"},"PeriodicalIF":4.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving effects of melatonin on memory and synaptic potentiation in a mouse model of Alzheimer's-like disease: the involvement of glutamate homeostasis and mGluRs receptors.","authors":"Narjes Khatoun Shabani Sadr, Fatemeh Bakhtiarzadeh, Koorosh Shahpasand, Javad Mirnajafi-Zadeh, Mehrdad Behmanesh","doi":"10.1186/s12993-025-00271-4","DOIUrl":"10.1186/s12993-025-00271-4","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is characterized by progressive cognitive decline and synaptic dysfunction, largely driven by amyloid plaques and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau. These pathological hallmarks disrupt glutamate signaling, which is essential for synaptic plasticity and memory consolidation. This study investigates the therapeutic potential of melatonin on memory and synaptic plasticity in an AD-like mouse model, with a focus on its regulatory effects on glutamate homeostasis and metabotropic glutamate receptors (mGluRs).</p><p><strong>Methods: </strong>The study began with an in-silico bioinformatics analysis of RNA-seq datasets from hippocampal tissues of AD patients to identify differentially expressed genes (DEGs) related to glutamate signaling and tau pathology. An AD-like model was induced via intra-hippocampal injection of cis-phospho tau in C57BL/6 mice. Memory function was assessed using behavioral tests. Synaptic plasticity was evaluated using in vitro field potential recording of hippocampal slices. Histological analyses included Nissl staining for neuronal density, Luxol Fast Blue for myelin integrity, and immunofluorescence for tau hyperphosphorylation. Molecular studies employed qPCR and Western blot to assess glutamate-related markers and tau phosphorylation. Melatonin (10 mg/kg) was administered intraperitoneally, starting either two weeks (early intervention) or four weeks (late intervention) post-induction.</p><p><strong>Results: </strong>Key molecular targets in glutamate signaling pathways were identified using bioinformatics. AD-like mice displayed memory deficits and synaptic dysfunction. Melatonin improved cognitive function, especially with early intervention, as confirmed by behavioral tests. Histological studies revealed reduced neuronal loss, improved myelin integrity, and decreased tau hyperphosphorylation. Molecular findings showed restored mGluR expression and reduced GSK3 activity. Early intervention yielded superior outcomes, with partial restoration of synaptic plasticity observed in LTP recordings.</p><p><strong>Conclusions: </strong>These findings underscore the neuroprotective properties of melatonin, mediated by its ability to modulate glutamate signaling and mGluR activity, offering new insights into its potential as a therapeutic agent for AD. Additionally, the results suggest that earlier administration of melatonin may significantly enhance its efficacy, highlighting the importance of timely intervention in neurodegenerative diseases.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"7"},"PeriodicalIF":4.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11916854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dopamine D1 receptor agonist alleviates post-weaning isolation-induced neuroinflammation and depression-like behaviors in female mice.","authors":"Zi-Wei Zhao, Yun-Chen Wang, Pei-Chun Chen, Shun-Fen Tzeng, Po-See Chen, Yu-Min Kuo","doi":"10.1186/s12993-025-00269-y","DOIUrl":"10.1186/s12993-025-00269-y","url":null,"abstract":"<p><strong>Background: </strong>Major depressive disorder is a significant global cause of disability, particularly among adolescents. The dopamine system and nearby neuroinflammation, crucial for regulating mood and processing rewards, are central to the frontostriatal circuit, which is linked to depression. This study aimed to investigate the effect of post-weaning isolation (PWI) on depression in adolescent mice, with a focus on exploring the involvement of microglia and dopamine D1 receptor (D1R) in the frontostriatal circuit due to their known links with mood disorders.</p><p><strong>Results: </strong>Adolescent mice underwent 8 weeks of PWI before evaluating their depression-like behaviors and the activation status of microglia in the frontostriatal regions. Selective D1-like dopamine receptor agonist SKF-81,297 was administered into the medial prefrontal cortex (mPFC) of PWI mice to assess its antidepressant and anti-microglial activation properties. The effects of SKF-81,297 on inflammatory signaling pathways were examined in BV2 microglial cells. After 8 weeks of PWI, female mice exhibited more severe depression-like behaviors than males, with greater microglial activation in the frontostriatal regions. Microglial activation in mPFC was the most prominent among the three frontostriatal regions examined, and it was positively correlated with the severity of depression-like behaviors. Female PWI mice exhibited increased expression of dopamine D2 receptors (D2R). SKF-81,297 treatment alleviated depression-like behaviors and local microglial activation induced by PWI; however, SKF-81,297 induced these alterations in naïve mice. In vitro, SKF-81,297 decreased pro-inflammatory cytokine release and phosphorylations of JNK and ERK induced by lipopolysaccharide, while in untreated BV2 cells, SKF-81,297 elicited inflammation.</p><p><strong>Conclusions: </strong>This study highlights a sex-specific susceptibility to PWI-induced neuroinflammation and depression. While targeting the D1R shows potential in alleviating PWI-induced changes, further investigation is required to evaluate potential adverse effects under normal conditions.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"6"},"PeriodicalIF":4.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the role of the brain-derived neurotrophic factor Val66Met polymorphism in repetitive mild traumatic brain injury outcomes in rats.","authors":"Lauren P Giesler, William T O'Brien, Jesse Bain, Gershon Spitz, Emily J Jaehne, Maarten van den Buuse, Sandy R Shultz, Richelle Mychasiuk, Stuart J McDonald","doi":"10.1186/s12993-025-00270-5","DOIUrl":"10.1186/s12993-025-00270-5","url":null,"abstract":"<p><strong>Background: </strong>Mild traumatic brain injury (mTBI) poses a significant public health concern, particularly regarding repetitive injury, with outcomes ranging from acute neurobehavioral deficits to long-term impairments. While demographic factors like age and sex influence outcomes, the understanding of genetic contributions, particularly the role of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, remains limited. This study aimed to characterize acute effects of repetitive mTBI (rmTBI) in rats with the Val68Met SNP, the rodent equivalent of the human Val66Met, focusing on behavioral, fluid biomarker, and histological changes.</p><p><strong>Methods: </strong>Using a closed-head injury model, rats underwent five mTBIs over consecutive days. Behavioral assessments included sensorimotor function, anxiety-like behavior, spatial learning and memory, and nociceptive response. Plasma neurofilament light (NfL) levels served as a biomarker of axonal injury and immunohistochemistry evaluated microglial activation.</p><p><strong>Results: </strong>Sensorimotor deficits and increased anxiety-like behavior were found in rats with rmTBI, but these changes were not affected by sex or genotype. Plasma NfL levels were higher in rmTBI compared with sham rats, with levels greater in female rmTBI when compared with male rmTBI rats. Microglial activation was observed in the hypothalamus of injured rats, but was not influenced by genotype or sex.</p><p><strong>Conclusions: </strong>While the Val68Met SNP did not significantly influence acute responses to rmTBI in this study, further investigation into alternative functional and pathophysiological outcomes, as well as long-term effects, is required.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"5"},"PeriodicalIF":4.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of TrkB-related induced metaplasticity within the BLA on anxiety, extinction learning, and plasticity in BLA-modulated brain regions.","authors":"Joyeeta Dutta Hazra, Kuldeep Shrivastava, Lisa-Sophie Wüstner, Rachel Anunu, Erez Chervinsky, Somoday Hazra, Simone Beuter, Martin Kriebel, Mouna Maroun, Hansjuergen Volkmer, Gal Richter-Levin","doi":"10.1186/s12993-025-00267-0","DOIUrl":"10.1186/s12993-025-00267-0","url":null,"abstract":"<p><strong>Background: </strong>Neuronal plasticity within the basolateral amygdala (BLA) is fundamental for fear learning. Metaplasticity, the regulation of plasticity states, has emerged as a key mechanism mediating the subsequent impact of emotional and stressful experiences. After mRNA knockdown of synaptic plasticity-related TrkB, we examined the impact of chronically altered activity in the rat BLA (induced metaplasticity) on anxiety-like behavior, fear memory-related behaviors, and neural plasticity in brain regions modulated by the BLA. These effects were investigated under both basal conditions and following exposure to acute trauma (UWT).</p><p><strong>Results: </strong>Under basal conditions, TrkB knockdown increased anxiety-like behavior and impaired extinction learning. TrkBKD also reduced LTP in the vSub-mPFC pathway but not in the dentate gyrus. Compared with those of control animals, acute trauma exposure led to increased anxiety-like behavior and impaired extinction learning in both the trauma-exposed group (CTR-UWT) and the trauma-exposed group on the background of TrkB knockdown (TrkBKD-UWT). However, the deficit in extinction learning was more pronounced in the TrkBKD-UWT group than in the CTR-UWT group. Accordingly, TrkBKD-UWT, but not CTR-UWT, resulted in impaired LTP in the vSub- mPFC pathway. Since LTP in this pathway is independent of BLA involvement, this result suggests that lasting intra-BLA-induced metaplasticity may also lead to transregional metaplasticity within the mPFC, as suggested previously.</p><p><strong>Conclusions: </strong>Taken together, these findings reveal the dissociative involvement of BLA function, on the one hand, in anxiety, which is affected by the knockdown of TrkB, and, on the other hand, in extinction learning, which is more significantly affected by the combination of intra-BLA-induced metaplasticity and exposure to emotional trauma.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"4"},"PeriodicalIF":4.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11874401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}