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Current Opinion in Neurobiology最新文献

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Calcium signaling at the interface between astrocytes and brain inflammation 星形胶质细胞与脑炎症界面的钙信号。
IF 4.8 2区 医学
Current Opinion in Neurobiology Pub Date : 2025-02-01 DOI: 10.1016/j.conb.2024.102940
Michaela M. Novakovic, Murali Prakriya
{"title":"Calcium signaling at the interface between astrocytes and brain inflammation","authors":"Michaela M. Novakovic,&nbsp;Murali Prakriya","doi":"10.1016/j.conb.2024.102940","DOIUrl":"10.1016/j.conb.2024.102940","url":null,"abstract":"<div><div>Astrocytes are the most prevalent glial cells of the brain and mediate vital roles in the development and function of the nervous system. Astrocytes, along with microglia, also play key roles in initiating inflammatory immune responses following brain injury, stress, or disease-related triggers. While these glial immune responses help contain and resolve cellular damage to the brain, dysregulation of astrocyte activity can in some cases amplify inflammation and worsen impact on neural tissue. As nonexcitable cells, astrocytes excitability is regulated primarily by Ca<sup>2+</sup> signals that control key functions such as gene expression, release of inflammatory mediators, and cell metabolism. In this review, we examine the molecular and functional architecture of Ca<sup>2+</sup> signaling networks in astrocytes and their impact on astrocyte effector functions involved in inflammation and immunity.</div></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"90 ","pages":"Article 102940"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Release your inhibitions: The cell biology of GABAergic postsynaptic plasticity 释放你的抑制：gaba能突触后可塑性的细胞生物学。
IF 4.8 2区 医学
Current Opinion in Neurobiology Pub Date : 2025-02-01 DOI: 10.1016/j.conb.2024.102952
Theresa M. Welle, Katharine R. Smith
{"title":"Release your inhibitions: The cell biology of GABAergic postsynaptic plasticity","authors":"Theresa M. Welle,&nbsp;Katharine R. Smith","doi":"10.1016/j.conb.2024.102952","DOIUrl":"10.1016/j.conb.2024.102952","url":null,"abstract":"<div><div>GABAergic synaptic inhibition controls circuit function by regulating neuronal plasticity, excitability, and firing. To achieve these goals, inhibitory synapses themselves undergo several forms of plasticity via diverse mechanisms, strengthening and weakening phasic inhibition in response to numerous activity-induced stimuli. These mechanisms include changing the number and arrangement of functional GABA<sub>A</sub>Rs within the inhibitory postsynaptic domain (iPSD), which can profoundly regulate inhibitory synapse strength. Here, we explore recent advances in our molecular understanding of inhibitory postsynaptic plasticity, with a focus on modulation of the trafficking, protein–protein interactions, nanoscale-organization, and posttranscriptional regulation of GABA<sub>A</sub>Rs and iPSD proteins. What has emerged is a complex mechanistic picture of how synaptic inhibition is controlled, with critical ramifications for cognition under typical and pathogenic conditions.</div></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"90 ","pages":"Article 102952"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Excitatory/Inhibitory imbalance as a mechanism linking autism and sleep problems 兴奋性/抑制性失衡是自闭症和睡眠问题之间的联系机制。
IF 4.8 2区 医学
Current Opinion in Neurobiology Pub Date : 2025-02-01 DOI: 10.1016/j.conb.2024.102968
Michelle C.D. Bridi , Lucia Peixoto
{"title":"Excitatory/Inhibitory imbalance as a mechanism linking autism and sleep problems","authors":"Michelle C.D. Bridi ,&nbsp;Lucia Peixoto","doi":"10.1016/j.conb.2024.102968","DOIUrl":"10.1016/j.conb.2024.102968","url":null,"abstract":"<div><div>Sleep problems occur more frequently in individuals with autism spectrum disorder (ASD) than in typically developing individuals, and recent studies support a genetic link between ASD and sleep disturbances. However, it remains unclear how sleep problems may be mechanistically connected to ASD phenotypes. A longstanding hypothesis posits that an imbalance between excitatory and inhibitory (E/I) signaling in the brain underlies the behavioral characteristics of ASD. In recent years, emerging evidence has shown that regulation of the E/I ratio is coupled to sleep/wake states in wild-type animal models. In this review, we will explore the idea of altered E/I regulation over the sleep/wake cycle as a mechanism bridging sleep disruption and behavioral phenotypes in ASD.</div></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"90 ","pages":"Article 102968"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The promise of cyclic AMP modulation to restore cognitive function in neurodevelopmental disorders 循环AMP调节恢复神经发育障碍患者认知功能的前景。
IF 4.8 2区 医学
Current Opinion in Neurobiology Pub Date : 2025-02-01 DOI: 10.1016/j.conb.2024.102966
Aniket Bhattacharya , Luka Turkalj , M. Chiara Manzini
{"title":"The promise of cyclic AMP modulation to restore cognitive function in neurodevelopmental disorders","authors":"Aniket Bhattacharya ,&nbsp;Luka Turkalj ,&nbsp;M. Chiara Manzini","doi":"10.1016/j.conb.2024.102966","DOIUrl":"10.1016/j.conb.2024.102966","url":null,"abstract":"<div><div>Cyclic AMP (cAMP) is a key regulator of synaptic function and is dysregulated in both neurodevelopmental (NDD) and neurodegenerative disorders. Due to the ease of diffusion and promiscuity of downstream effectors, cAMP signaling is restricted within spatiotemporal domains to localize activation. Among the best-studied mechanisms is the feedback inhibition of cAMP-dependent protein kinase (PKA) activity by phosphodiesterases 4 (PDE4s) at synapses controlling neuronal plasticity, which is largely regulated by PDE4D. In fact, genetic variants in genes for multiple PKA subunits and PDE4D lead to NDDs. Here, we discuss the rationale for choosing PDE4D as a candidate for the design of selective allosteric inhibitors and the recent advances in clinical trials. These new compounds improve cognitive function in preclinical animal models due to improved selectivity and more physiological inhibition of the active enzyme. We also discuss opportunities for better understanding of PDE4D function in general, and for the development of next-generation inhibitors.</div></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"90 ","pages":"Article 102966"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CaMKII mechanisms that promote pathological LTP impairments.
IF 4.8 2区 医学
Current Opinion in Neurobiology Pub Date : 2024-12-31 DOI: 10.1016/j.conb.2024.102961
Matthew E Larsen, Nicole L Rumian, Nidia Quillinan, K Ulrich Bayer
{"title":"CaMKII mechanisms that promote pathological LTP impairments.","authors":"Matthew E Larsen, Nicole L Rumian, Nidia Quillinan, K Ulrich Bayer","doi":"10.1016/j.conb.2024.102961","DOIUrl":"https://doi.org/10.1016/j.conb.2024.102961","url":null,"abstract":"<p><p>The Ca<sup>2+</sup>/calmodulin-dependent protein kinase II (CaMKII) is extremely abundant in the brain, where it prominently mediates hippocampal long-term potentiation (LTP), a form of synaptic plasticity thought to be required for learning and memory. However, CaMKII also mediates LTP impairments related to Alzheimer's disease (AD) and global cerebral ischemia (GCI), two conditions that are very distinct but are both associated with impairments in learning and memory. In both cases, CaMKII inhibitors prevented these LTP impairments. Thus, CaMKII actively mediates both physiological LTP and the pathological LTP impairments related to AD and GCI. Notably, these active LTP impairment mechanisms are in stark contrast to other conditions, like normal aging, where milder LTP impairments are caused instead by passive lack of CaMKII function.</p>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":" ","pages":"102961"},"PeriodicalIF":4.8,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Revisiting the genetic architecture of autism spectrum disorders in the genomic era: Insights from East Asian studies 在基因组时代重新审视自闭症谱系障碍的遗传结构：来自东亚研究的见解
IF 4.8 2区 医学
Current Opinion in Neurobiology Pub Date : 2024-11-30 DOI: 10.1016/j.conb.2024.102936
Zilong Qiu, Ailian Du
{"title":"Revisiting the genetic architecture of autism spectrum disorders in the genomic era: Insights from East Asian studies","authors":"Zilong Qiu,&nbsp;Ailian Du","doi":"10.1016/j.conb.2024.102936","DOIUrl":"10.1016/j.conb.2024.102936","url":null,"abstract":"<div><div>This review delves into the genetic landscape of Autism Spectrum Disorder (ASD) in the genomic era, with a special focus on insights from East Asian populations. We analyze a spectrum of genetic research, including whole-exome and whole-genome sequencing, to elucidate both the challenges and advancements in comprehending the genetic foundations of ASD. Critical findings from this review highlight the identification of <em>de novo</em> variants, particularly noting the significant role of rare variants that differ from the common variants identified in earlier research. The review emphasizes the importance of large, diverse, and meticulously maintained ASD cohorts, which are essential for advancing genetic studies and developing potential therapeutic interventions. Through collaborative international efforts, we argue for a global perspective necessary to grasp the intricate genetic factors underlying ASD.</div></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"90 ","pages":"Article 102936"},"PeriodicalIF":4.8,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Editorial overview: Addiction 编辑概述：成瘾
IF 4.8 2区 医学
Current Opinion in Neurobiology Pub Date : 2024-11-28 DOI: 10.1016/j.conb.2024.102933
Mariella De Biasi, Gavan McNally
{"title":"Editorial overview: Addiction","authors":"Mariella De Biasi,&nbsp;Gavan McNally","doi":"10.1016/j.conb.2024.102933","DOIUrl":"10.1016/j.conb.2024.102933","url":null,"abstract":"","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"90 ","pages":"Article 102933"},"PeriodicalIF":4.8,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Construction destruction: Contribution of dyregulated proteostasis to neurodevelopmental disorders 结构破坏：蛋白质平衡失调对神经发育障碍的贡献
IF 4.8 2区 医学
Current Opinion in Neurobiology Pub Date : 2024-11-28 DOI: 10.1016/j.conb.2024.102934
Kellen D. Winden, Juan F. Ruiz, Mustafa Sahin
{"title":"Construction destruction: Contribution of dyregulated proteostasis to neurodevelopmental disorders","authors":"Kellen D. Winden,&nbsp;Juan F. Ruiz,&nbsp;Mustafa Sahin","doi":"10.1016/j.conb.2024.102934","DOIUrl":"10.1016/j.conb.2024.102934","url":null,"abstract":"<div><div>Genetic causes of neurodevelopmental disorders (NDDs) such as epilepsy and autism spectrum disorder are rapidly being uncovered. The genetic risk factors that are responsible for various NDDs fall into many categories, and while some genes such as those involved in synaptic transmission are expected, there are several other classes of genes whose involvement in these disorders is not intuitive. One such group of genes is involved in protein synthesis and degradation, and the balance between these opposing pathways is termed proteostasis. Here, we review these pathways, the genetics of the related neurological disorders, and some potential disease mechanisms. Improved understanding of this collection of genetic disorders will be informative for the pathogenesis of these disorders and imply novel therapeutic strategies.</div></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"90 ","pages":"Article 102934"},"PeriodicalIF":4.8,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impacts of adverse childhood experiences on individuals with autism spectrum disorder 童年不良经历对自闭症谱系障碍患者的影响
IF 4.8 2区 医学
Current Opinion in Neurobiology Pub Date : 2024-11-06 DOI: 10.1016/j.conb.2024.102932
Tsutomu Takeda , Manabu Makinodan , Michihiro Toritsuka , Nakao Iwata
{"title":"Impacts of adverse childhood experiences on individuals with autism spectrum disorder","authors":"Tsutomu Takeda ,&nbsp;Manabu Makinodan ,&nbsp;Michihiro Toritsuka ,&nbsp;Nakao Iwata","doi":"10.1016/j.conb.2024.102932","DOIUrl":"10.1016/j.conb.2024.102932","url":null,"abstract":"<div><div>Individuals with autism spectrum disorder (ASD) are more likely to experience adverse childhood experiences (ACEs) compared with typically developing (TD) individuals, which predisposes them to an elevated risk of mental health issues. This review elucidates the profound impact of ACEs on individuals with ASD by synthesizing findings from a plethora of epidemiologic and biological studies, encompassing genetics, epigenetics, and neuroimaging. Despite the limited number of studies explicitly focusing on this intersection, the extant literature consistently demonstrates that ASD individuals are disproportionately affected by ACEs, leading to significant deterioration in mental health and brain function. Furthermore, the nature and extent of the effects of ACEs appear to diverge between ASD and TD populations, underscoring the necessity for tailored clinical and research approaches. Understanding these complex and intertwined interactions is imperative for advancing both clinical practice and research, with the goal of mitigating the adverse outcomes associated with ACEs in ASD individuals.</div></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"89 ","pages":"Article 102932"},"PeriodicalIF":4.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
On the targeting of voltage-gated calcium channels to neurotransmitter release sites 电压门控钙通道在神经递质释放点的定位
IF 4.8 2区 医学
Current Opinion in Neurobiology Pub Date : 2024-11-04 DOI: 10.1016/j.conb.2024.102931
Morven Chin, Pascal S. Kaeser
{"title":"On the targeting of voltage-gated calcium channels to neurotransmitter release sites","authors":"Morven Chin,&nbsp;Pascal S. Kaeser","doi":"10.1016/j.conb.2024.102931","DOIUrl":"10.1016/j.conb.2024.102931","url":null,"abstract":"<div><div>At the presynaptic active zone, voltage-gated Ca<sup>2+</sup> channels (Ca<sub>V</sub>s) mediate Ca<sup>2+</sup> entry for neurotransmitter release. Ca<sub>V</sub>s are a large family of proteins, and different subtypes have distinct localizations across neuronal somata, dendrites and axons. Here, we review how neurons establish and maintain a specific Ca<sub>V</sub> repertoire at their active zones. We focus on molecular determinants for cargo assembly, presynaptic delivery and release site tethering, and we discuss recent work that has identified key roles of the Ca<sub>V</sub> intracellular C-terminus. Finally, we evaluate how these mechanisms may differ between different types of neurons. Work on Ca<sub>V</sub>s provides insight into the protein targeting pathways that help maintain neuronal polarity.</div></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"89 ","pages":"Article 102931"},"PeriodicalIF":4.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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