Behavioral and Brain Functions最新文献

{"title":"TREK-1 and epilepsy: regulating the balance of K⁺ and the glutamate release in astrocyte-neuron interactions.","authors":"Jianing Yang, Li Li, Yanan Xu, Yuguang Guan, Xiaoli Li","doi":"10.1186/s12993-025-00294-x","DOIUrl":"https://doi.org/10.1186/s12993-025-00294-x","url":null,"abstract":"<p><p>The TWIK-related K⁺ channel (TREK-1), a member of the two-pore domain potassium(K2P) family, is characterized as a \"leaky potassium channel\" and is integral to the maintenance of the resting membrane potential. As the most abundant cell type in the central nervous system, astrocytes play important roles in the development of epilepsy by regulating the release of glutamate and the function of potassium channels. Previous studies have revealed that TREK-1 is involved in a range of neurological diseases, including epilepsy. In astrocytes, TREK-1 acts as a crucial regulator of the rapid release of glutamate and passive conductance. However, controversy remains about the expression levels of TREK-1-binding receptors in the process of the release and recycling of glutamate in tripartite synapses. Thus, elucidating the pathological mechanisms involving TREK-1 in epilepsy could significantly increase our understanding of the pathophysiological basis of diseases and facilitate the identification of potential targets for novel therapeutic interventions. Here, we review the physiological function of TREK-1 and studies examining the role of TREK-1 in epilepsy, with a particular emphasis on its interactions with glutamate at tripartite synapses. Furthermore, we provide an analysis of the associated molecular mechanisms of this channel and conclude with an outlook on impending studies on TREK-1 as a novel therapeutic target for epilepsy.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"27"},"PeriodicalIF":3.3,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940458","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":"Behavioral variant frontotemporal dementia as a model for understanding the cognitive and cerebral determinants of verbal creativity.","authors":"Victor Altmayer, Marcela Ovando-Tellez, Théophile Bieth, Bénédicte Batrancourt, Armelle Rametti-Lacroux, Lucy Bernardaud, Sarah Moreno-Rodriguez, Lucie Vigreux, Vincent Ledu, Béatrice Garcin, Raffaella Migliaccio, Isabelle Le Ber, Alizée Lopez-Persem, Richard Levy, Emmanuelle Volle","doi":"10.1186/s12993-025-00292-z","DOIUrl":"https://doi.org/10.1186/s12993-025-00292-z","url":null,"abstract":"<p><strong>Background: </strong>Although creativity is an essential cognitive function to adapt to an ever-changing world, its neurocognitive and cerebral bases still need clarification. Current models highlight the interaction between associative and executive processes underpinned by the default mode (DMN), executive control (ECN) and salience networks (SN). Furthermore, recent neuroimaging studies highlight the key role of the prefrontal cortex (PFC), located at the crossroads of these networks. Hence, behavioral variant frontotemporal dementia (bvFTD), characterized by progressive neurodegeneration principally impacting the prefrontal cortex and the intrinsic connectivity of these three creativity-related networks, represents a unique model to study creativity. In this study involving 14 bvFTD patients and 20 matched controls, we used a simple word-to-word association task (FGAT) to explore the specific cognitive processes involved in remote thinking, i.e., the production of creative semantic associations. Using voxel-based morphometry, we uncovered critical brain regions for each component and then characterized these regions' intrinsic connectivity profiles using resting-state functional connectivity in healthy controls.</p><p><strong>Results: </strong>We dissociated four key cognitive components underlying remote thinking: spontaneous associative thinking, inhibition of unoriginal responses, intentional remote associative thinking, and verbal initiation; and replicated them in three independent datasets. Spontaneous associative thinking relied on temporal and cerebellar regions involved in low-order and automatic semantic processing, connected with the DMN, ECN and SN. Inhibition of prepotent unoriginal responses depended on key nodes of the SN. The ability to intentionally generate remote semantic associations was underpinned by key regions of the DMN. Finally, initiation of verbal responses relied on the right dorsolateral PFC, connected to the ECN. BvFTD patients were impaired in the last three components. Two components, cognitive inhibition and intentional remote thinking, mediated the link between atrophy in critical regions and an independent measure of creative abilities.</p><p><strong>Conclusions: </strong>These findings advance our understanding of creative neurocognition, distinguishing components of creative thinking and clarifying their critical cerebral bases, and participate in the characterization of creativity impairment in patients with bvFTD.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"26"},"PeriodicalIF":3.3,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940430","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":"C18:0 GM3 ganglioside's efficacy in LPS-induced parkinsonism: neuroprotection, inflammatory inhibition and gliosis mitigation.","authors":"Tsung-Ta Liu, Cheng-Tsung Liu, I-Hsun Li, Yu-Chieh Chu, Hao-Yuan Hung, Chuang-Hsin Chiu, Ta-Kai Chou, Shiao-Yun Li, Tin-An Wang, Jui-Hu Shih","doi":"10.1186/s12993-025-00289-8","DOIUrl":"10.1186/s12993-025-00289-8","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is an incurable neurological disorder, and current pharmacological therapies primarily address symptoms without halting disease progression. Emerging evidence highlights PD as a neuroinflammatory disease, with chronic brain inflammation preceding the onset of motor dysfunction. This study investigates the role of C18:0 GM3, a long-chain fatty acids-containing ganglioside, in modulating inflammatory responses in PD, exploring its therapeutic potential in mitigating LPS-induced parkinsonism.</p><p><strong>Methods: </strong>Male C57BL/6 mice were utilized in an LPS-induced PD model to evaluate the neuroprotective effects of C18:0 GM3 ganglioside. Pre-treatment with C18:0 GM3 was assessed through behavioral tests, including rotarod and beam-walking, to determine motor function improvements. Dopaminergic neurotoxicity was quantified using [¹⁸F]FE-PE2I positron emission tomography (PET) imaging and tyrosine hydroxylase (TH) staining. The anti-inflammatory and anti-gliosis effects of C18:0 GM3 were analyzed by measuring cytokine levels (IL-1β, TNF-α) and by assessing Iba1 and GFAP immunoreactivity as indicators of microglial and astrocytic changes, respectively.</p><p><strong>Results: </strong>Pre-treatment with C18:0 GM3 ganglioside significantly enhanced motor coordination and balance, as evidenced by improved performance in rotarod and beam-walking tests. Furthermore, C18:0 GM3 ganglioside effectively attenuated LPS-induced dopaminergic neurotoxicity, evidenced by increased striatal dopamine transporter availability on [¹⁸F]FE-PE2I PET imaging and the preservation of TH-positive neurons in the striatum. In addition, C18:0 GM3 markedly suppressed the expression of pro-inflammatory cytokines, including IL-1β and TNF-α, along with cyclooxygenase-2 levels. C18:0 GM3 also reduced gliosis, as demonstrated by a decrease in Iba1-positive microglial cells and GFAP-positive astrocytes.</p><p><strong>Conclusion: </strong>Our data indicate that C18:0 GM3 primarily attenuates the TLR4-driven inflammatory cascade initiated by intrastriatal LPS, thereby secondarily preserving striatal dopaminergic terminals and improving motor deficits. Although these results highlight anti-inflammatory neuroprotection, additional studies are required to determine whether GM3 also modulates downstream Parkinson-specific processes such as α-synuclein aggregation or progressive neurodegeneration.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"25"},"PeriodicalIF":3.3,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717299","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":"Role of astrocytic mu-opioid receptors of the ventrolateral periaqueductal gray in modulating anxiety-like responses.","authors":"Yinan Du, Aozhuo Zhang, Zhiwei Li, Yukui Zhao, Shuyi Liu, Chunling Wei, Qiaohua Zheng, Yanning Qiao, Yihui Liu, Wei Ren, Jing Han, Zhiqiang Liu, Fei Gao","doi":"10.1186/s12993-025-00291-0","DOIUrl":"10.1186/s12993-025-00291-0","url":null,"abstract":"<p><strong>Background: </strong>Mu-opioid receptors (MORs) are critical regulators mediating the modulation of several behavioral reactions, including analgesia, addiction, and sedation. Recent studies have reported that MORs are closely associated with mood disorders or anxiety behaviors; however, the underlying neural mechanisms remain unclear. The periaqueductal gray (PAG), a key brain area, participates in the modulation of aversive emotional behaviors. MORs show a high expression in the ventrolateral PAG (vlPAG) region. This study explored the preliminary role of MORs expressed in the vlPAG in modulating emotional behaviors.</p><p><strong>Results: </strong>Bilateral administration of DAMGO, an MOR-specific agonist, into the vlPAG of male mice elicited anxiety-like behaviors in elevated plus maze tests. This phenotype was reversed by conditional knockdown of astrocytic MORs. In contrast, glutamatergic or GABAergic MORs were not involved in vlPAG MOR-dependent anxiety-like behaviors. By using in vitro calcium imaging of vlPAG astrocytes and chemical genetic technologies, we found that vlPAG astrocytic MORs can promote astrocytic calcium signaling, which can efficiently induce anxiety-like behaviors. Accordingly, the interference of astrocytic calcium signaling by viral infection reversed vlPAG-dependent anxiety-like behaviors.</p><p><strong>Conclusion: </strong>Our findings demonstrated that vlPAG astrocytic, but not glutamatergic or GABAergic, MORs are involved in modulating emotional reactions, and these effects are accomplished by MOR-elicited astrocytic calcium signaling mechanisms. The present study provides a theoretical basis for treating emotional dysfunctions during MOR-targeted management.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"24"},"PeriodicalIF":3.3,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697505","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":"Chronic lipopolysaccharide exposure promotes cognitive impairments by activating TRPC6-AIM2 inflammasome signaling and the regulation of ginsenoside Rg1 in Trpc6^-/- mice.","authors":"Yinglin Fu, Hui Zhang, Xing Zhu, Haoyu Liang, Lei Fan, Yong Su, Weiping Li, Weizu Li","doi":"10.1186/s12993-025-00290-1","DOIUrl":"10.1186/s12993-025-00290-1","url":null,"abstract":"<p><strong>Background: </strong>Chronic neuroinflammation is a pivotal pathogenesis in neurodegenerative diseases (NDDs). Transient receptor potential canonical protein 6 (TRPC6) has an essential role in the maintenance of calcium homeostasis in cells. Our previous study indicated that TRPC6 signaling is involved in Aβ deposition and NLRP1 inflammasome activation in type 2 diabetes mellitus-associated cognitive dysfunction. However, whether TRPC6 signaling contributes to chronic lipopolysaccharide (LPS)-induced neuroinflammatory injury and the mechanism remain unclear.</p><p><strong>Methods: </strong>In this study, male mice received intraperitoneal injections of LPS (200 µg/kg) for 21 days to induce a chronic neuroinflammation model. The open field test, hole-board test, and Morris water maze were conducted to evaluate cognitive function. The H&E and Nissl staining was employed to examine neuronal injury. The immunofluorescence, western blotting, or q-PCR were used to analyze TRPC6, AIM2 inflammasome expression, and Nrf2 activation. The fluorescent probes and calcium imaging were performed to assess ROS accumulation and calcium dysregulation in LPS-induced HT22 neuron cells.</p><p><strong>Results: </strong>Chronic LPS exposure induced behavioral deficits in locomotion, exploratory behavior, and learning and memory, and neuronal damages with less expressions of PSD95 and Synaptophysin in mice. Mechanistically, LPS exposure significantly increased ROS production, TRPC6 expression and calcium overload, and induced AIM2 inflammasome activation in vivo or in vitro. While Trpc6 knockout could significantly improve LPS-induced cognitive dysfunction and neuronal injuries, inhibit TRPC6-mediated calcium overload, and downregulate the expressions of AIM2, caspase-1, IL-1β, IL-6, caspase-3 and Bax in vivo or in vitro. Additionally, Rg1 treatment significantly inhibited calcium overload and AIM2 inflammasome activation in LPS-induced HT22 cells. More importantly, Rg1 significantly activated Nrf2 signaling and reduced ROS production in LPS-induced mice or HT22 cells.</p><p><strong>Conclusions: </strong>Trpc6 knockout can improve chronic LPS-induced neuroinflammation and injury by inhibiting TRPC6-AIM2 inflammasomes. While Rg1 treatment can alleviate LPS-induced neuroinflammation and injury not only by inhibiting TRPC6-AIM2 inflammasomes activation but also activating Nrf2 signaling.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"23"},"PeriodicalIF":3.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688824","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":"Behavioral phenotyping identifies autism-like repetitive stereotypies in a Tsc2 haploinsufficient rat model.","authors":"Antonia Ramme, Mirjam Zachow, Bettina Habelt, Iveta Vojtechova, Tomas Petrasek, Robert Waltereit, Nadine Bernhardt","doi":"10.1186/s12993-025-00284-z","DOIUrl":"10.1186/s12993-025-00284-z","url":null,"abstract":"<p><p>Besides deficits in social communication and interaction, repetitive behavior patterns are core manifestations of autism spectrum disorder (ASD). Phenotypes are heterogeneous and can range from simple lower-order motor stereotypies to more complex higher-order cognitive inflexibility and fixated interests. Due to ASD's multifaceted etiology, animal models are often generated from monogenic diseases associated with ASD, such as Tuberous Sclerosis Complex (TSC), and are expected to copy behavioral core deficits to increase the model´s translational value for ASD disease research and novel treatment development. The global haploinsufficient Tsc2^+/- Eker rat model has been shown to display ASD core symptoms in the social domain. However, the presence and extent of aberrant repetitive behavior patterns in the Eker rat remain to be investigated. Thus, the present study applied a set of behavioral tests to determine the repetitive behavioral profile in Tsc2^+/- Eker rats and used brain-region-specific neurotransmitter analysis to support findings on a molecular level. Tsc2^+/- animals demonstrated lower-order repetitive behavior in the form of excessive self-grooming and nestlet shredding under non-stressful conditions that co-occurred alongside social interaction deficits. However, no higher-order repetitive behavior was detected in Tsc2^+/- rats. Interestingly, Tsc2^+/- rats exhibited increased levels of homeostatic dopamine in the prefrontal cortex, supporting the link between aberrant cortical dopaminergic transmission and the appearance of lower-order repetitive phenotypes. Together, our results support the Tsc2^+/- Eker rat as a model of ASD-like behavior for further investigation of ASD-related development and neurobiology.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"20"},"PeriodicalIF":4.7,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12225118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558914","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 gut microbiome and metabolomic alterations underlying colitis-induced encephalopathy in mice: mechanistic insight.","authors":"Aimin Cai, Dingchao Shen, Qiushuang Xiong, Shize Li, Chenyu Qiu, Lele Li, Zhiwei Chen, Xinlu Lin, Qing Yao, Youting Zhang, Ruijie Chen, Longfa Kou","doi":"10.1186/s12993-025-00283-0","DOIUrl":"10.1186/s12993-025-00283-0","url":null,"abstract":"<p><strong>Background: </strong>In addition to classical gastrointestinal symptoms, patients with inflammatory bowel disease (IBD) often exhibit neurological manifestations, such as mood disorders and cognitive dysfunctions, which are frequently overlooked. However, the potential pathogenesis of IBD-related encephalopathy remains unclear, and few studies have explored the influence of interactions between the gut microbiota and the host gut-brain metabolome on the emergence of brain diseases in IBD mice. In this study, we conducted a comprehensive analysis of gut microbiome and metabolome alterations in dextran sulfate sodium salt (DSS)-induced IBD mice compared to control mice, focusing on colonic contents and hippocampal tissue. Our aim was to investigate the putative mechanisms underlying the microbiota-gut-brain axis in IBD-induced encephalopathy.</p><p><strong>Results: </strong>IBD mice showed depression-like behaviors and cognitive deficits. Metabolic profiling revealed distinct patterns in the colonic contents and hippocampal areas of IBD mice, marked by decreased energy metabolism, amino acid levels, short-chain fatty acids (SCFAs), and choline metabolism. These metabolic changes were negatively associated with the abundance of Bacteroides, Turicibacter, Ruminococcus, and Akkermansia, while Desulfovibrio and Lactobacillus showed positive correlations.</p><p><strong>Conclusions: </strong>This study identifies unique microbial and gut-brain metabolite signatures associated with DSS-induced changes and offers new metabolic insights into the microbiota-gut-brain axis in IBD-related brain disorders. It highlights the potential of targeting gut microbiota to modulate host metabolism as a therapeutic approach for IBD-related neurological complications.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"17"},"PeriodicalIF":4.7,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282314","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":"Combined enriched environment and fluoxetine enhance myelin protein expression in the prefrontal cortex of a chronic unpredictable stress depression model.","authors":"Jingyang Gu, Cong Liu, Yan Li, Laipeng Feng, Mengjun Geng, Jiao Dong, Jinhong Han, Liqin Zhao, Qiujing Shao, Hui-Ying Wang, Chang-Hong Wang","doi":"10.1186/s12993-025-00282-1","DOIUrl":"10.1186/s12993-025-00282-1","url":null,"abstract":"<p><strong>Background: </strong>The primary protein components of white matter include myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP). Alterations in their expression are significantly implicated in depression. This study investigated changes in MBP and CNP expression associated with depressive-like behaviors induced by chronic unpredictable stress (CUS) and evaluated therapeutic interventions using fluoxetine (FLU), an enriched environment (EE), or their combination.</p><p><strong>Methods: </strong>Male Sprague Dawley rats were randomly assigned to a control group and four CUS-exposed groups undergoing 6 weeks of stress. During the final 3 weeks of CUS, rats received daily fluoxetine (CUS + FLU group), were housed in EE (CUS + EE group), or received combined EE and fluoxetine (CUS + FLU + EE group). Depression-like behaviors were assessed through sucrose preference, forced swimming, and open field tests after CUS completion and at the end of weeks 4-6. Protein and mRNA expression levels of MBP and CNP in the prefrontal cortex were quantified via immunohistochemistry, western blot, and qRT-PCR.</p><p><strong>Results: </strong>Three weeks following CUS exposure, rats demonstrated significant depression-like behavioral phenotypes. By the fifth week, these behavioral deficits were ameliorated in the CUS + FLU + EE, whereas the CUS + FLU and CUS + EE groups exhibited comparable behavioral recovery by week 6. Parallel molecular analyses revealed diminished protein and mRNA expression levels of MBP and CNP in the prefrontal cortex of CUS-exposed animals, accompanied by a pronounced elevation in IL-1β expression. Therapeutic interventions with FLU, EE, or their combination significantly attenuated these CUS-induced molecular alterations.</p><p><strong>Conclusions: </strong>The antidepressant effects correlated with restored MBP, CNP, and IL-1β expression levels, suggesting that MBP/CNP deficiencies in depression may involve IL-1β elevation. In particular, combined enriched environment and fluoxetine accelerated behavioral recovery.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"16"},"PeriodicalIF":4.7,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274128","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":"Unraveling genetic risk contributions to nonverbal status in autism spectrum disorder probands.","authors":"Huan Liu, Shenghan Wang, Binbin Cao, Jijun Zhu, Zhifang Huang, Pan Li, Shunjie Zhang, Xian Liu, Jing Yu, Zhongting Huang, Linzhuo Lv, Fuqiang Cai, Weixin Liu, Zhijian Song, Yuxin Liu, Tao Pang, Suhua Chang, Ying Chen, Junfang Chen, Wen-Xiong Chen","doi":"10.1186/s12993-025-00278-x","DOIUrl":"10.1186/s12993-025-00278-x","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) presents a wide range of cognitive and language impairments. In this study, we investigated the genetic basis of non-verbal status in ASD using a comprehensive genomic approach. We identified a novel common variant, rs1944180 in CNTN5, significantly associated with non-verbal status through family-based Transmission Disequilibrium Testing. Polygenic risk score (PRS) analysis further showed that higher ASD PRS was significantly linked to non-verbal status (p = 0.034), specific to ASD and not related to other conditions such as bipolar disorder, schizophrenia and three language-related traits. Using structural equation modeling (SEM), we found two causal SNPs, rs1247761 located in KCNMA1 and rs2524290 in RAB3IL1, linking ASD with language traits. The model indicated a unidirectional effect, with ASD driving language impairments. Additionally, de novo mutations (DNMs) were found to be related with ASD and interaction between common variants and DNMs significantly impacted non-verbal status (p = 0.038). Our findings also identified 5 high-risk ASD genes, and DNMs were enriched in glycosylation-related pathways. These results offer new insights into the genetic mechanisms underlying language deficits in ASD.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"15"},"PeriodicalIF":4.7,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246214","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":"Neurodegeneration models in Parkinson's disease: cellular and molecular paths to neuron death.","authors":"Diana D Álvarez-Luquín, Rubén R González-Fernández, Martin E Torres-Velasco, Eduardo Ichikawa-Escamilla, Asiel Arce-Sillas, Eduardo Martínez-Martínez, Clara L Miranda-Narvaez, Juan F Rodríguez-Ramírez, Laura Adalid-Peralta","doi":"10.1186/s12993-025-00279-w","DOIUrl":"10.1186/s12993-025-00279-w","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects dopaminergic neurons in the substantia nigra pars compacta. It is a complex disease that is strongly influenced by environmental and genetic factors. While the exact causes of PD are not well understood, research on the effects of toxic substances that induce neuronal death has shed some light on the etiology of the disease. In addition, studies have implicated protein aggregation and impaired mitochondrial, endoplasmic reticulum (ER), proteasome, and/or lysosomal function in the pathogenesis of PD. This review focuses on the alterations in intraneuronal organelles and the role of toxic agents that lead to organelle damage and neurodegeneration that characterize PD. We describe in vivo and in vitro models that have been used to elucidate the factors that lead to the death of dopaminergic neurons and summarize the molecular mechanisms that may underlie the changes that promote neurodegeneration. A deeper understanding of the mechanisms of neuronal death may help us to develop new therapies and interventions to delay or prevent the progression of PD.</p>","PeriodicalId":8729,"journal":{"name":"Behavioral and Brain Functions","volume":"21 1","pages":"14"},"PeriodicalIF":4.7,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191428","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}