{"title":"Inner Ear Organoids: A Hydrogel-Based Platform for Drug Screening and Deafness Modeling.","authors":"Yuyu Cao, Xiaotao Liu, Renjie Chai, Zuhong He","doi":"10.1007/s12264-025-01479-0","DOIUrl":"https://doi.org/10.1007/s12264-025-01479-0","url":null,"abstract":"<p><p>This review highlights advances in inner ear organoids (IEOs) as a novel platform for drug screening and disease modeling, particularly for hearing loss. IEOs, derived from embryonic stem cells, induced pluripotent stem cells, or tissue-specific progenitors, provide a physiologically relevant alternative to traditional animal models. Significant progress has been made in utilizing various cell sources, extracellular matrix materials such as Matrigel and hydrogels, and methods for controlling microenvironments through biochemical and biophysical signals. Applications of IEOs in drug screening, disease modeling, and personalized medicine enable exploration of hearing loss mechanisms and therapeutic testing. However, challenges remain, including the incomplete maturation of cochlear cells and difficulty replicating in vivo environments. Future research should focus on optimizing IEO generation, incorporating microfluidic technologies, and advancing high-throughput screening to enhance drug discovery and clinical translation.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337302","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}
{"title":"Selectively Labeling and Distinguishing Adrenergic and Noradrenergic Neurons in the Sympathetic Nervous System.","authors":"Guodong Pang, Yuyan Shi, Jiayi Shen, Tianyu Shao, Fengchao Wang, Yijing Wang, Cheng Zhan","doi":"10.1007/s12264-025-01522-0","DOIUrl":"https://doi.org/10.1007/s12264-025-01522-0","url":null,"abstract":"<p><p>The sympathetic nervous system, with adrenaline and noradrenaline as key neurotransmitters, plays a vital role in regulating physiological functions. However, distinguishing between adrenergic and noradrenergic neurons has been challenging. This study used CRISPR/Cas9 technology to generate Net-Cre and Pnmt-p2a-Cre transgenic mouse lines. The results showed that gene editing did not affect the normal reproduction and development of these mice, and their stress levels were comparable to those of wild-type mice. In the central nervous system (CNS), noradrenergic neurons are distributed mainly in the brainstem and other regions, whereas adrenergic neurons are distributed specifically in the ventrolateral medulla (VLM) and the nucleus of the solitary tract (NTS). In the peripheral nervous system (PNS), more than 98% of neurons in the sympathetic ganglia are noradrenergic. AAV-based tracing of the locus coeruleus (LC) revealed that LC noradrenaline transporter (NET) neurons had extensive long-distance projections, whereas phenylethanolamine-N-methyltransferase (PNMT) neurons had short-range projections. These transgenic mouse lines provide a powerful tool for further research on the functions of adrenergic and noradrenergic neurons and the sympathetic nervous system.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318610","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}
Yan Zhang, Junzhao Li, Xueju Wang, Zhongyu Zhang, Shuai Long, Chuanyu Edward Li, Yan Liu, John Man Tak Chu, Raymond Chuen-Chung Chang, Gordon Tin-Chun Wong, Yong Zhang
{"title":"Modulation of Glutamate Release by Dexmedetomidine Preserves Dendritic Spines and Alleviates Cognitive Impairment in a Murine Model of Perioperative Neurocognitive Disorder.","authors":"Yan Zhang, Junzhao Li, Xueju Wang, Zhongyu Zhang, Shuai Long, Chuanyu Edward Li, Yan Liu, John Man Tak Chu, Raymond Chuen-Chung Chang, Gordon Tin-Chun Wong, Yong Zhang","doi":"10.1007/s12264-025-01518-w","DOIUrl":"https://doi.org/10.1007/s12264-025-01518-w","url":null,"abstract":"<p><p>Perioperative neurocognitive disorders (PNDs) represent a significant challenge in the perioperative setting, while the pathophysiology of PNDs remains unclear. Utilizing a murine model of abdominal surgery, we found that abnormal glutamatergic neurotransmission in the medial prefrontal cortex (mPFC) and hippocampus contributes to postoperative cognitive impairments. Increases in the frequency of miniature excitatory postsynaptic currents in both the mPFC and CA1 neurons indicate enhanced presynaptic glutamate release while having little effect on inhibitory neurotransmission. Surgery also enhances glutamate release from presynaptic terminals in the Schaffer collateral pathway. In addition, abdominal surgery increased the activation of microglia and astrocytes, elevated central inflammatory markers, and reduced excitatory amino-acid transporter-2 expression. Dexmedetomidine significantly mitigates the postoperative cognitive deficits by reducing inflammation and preserving neuronal structural complexity and dendritic spine stability, likely through inhibiting glutamate release and enhancing its reuptake. These findings advance our understanding of the etiology of PNDs and provide hints for potential intervention.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308724","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}
António E Abreu, Nuno Empadinhas, Sandra Morais Cardoso
{"title":"Unveiling Butyrate as a Parkinson's Disease Therapy.","authors":"António E Abreu, Nuno Empadinhas, Sandra Morais Cardoso","doi":"10.1007/s12264-025-01498-x","DOIUrl":"https://doi.org/10.1007/s12264-025-01498-x","url":null,"abstract":"<p><p>Butyrate, a short-chain fatty acid (SCFA) produced by gut microbiota, plays crucial roles in maintaining intestinal homeostasis and modulating the gut-brain axis. Dysbiosis and SCFA imbalances are increasingly recognized as contributors to disease pathogenesis. A decrease in butyrate-producing bacteria leads to reduced butyrate levels, which have been linked to increased intestinal permeability, systemic inflammation, and neuroinflammation. Emerging evidence highlights a potential therapeutic role for butyrate in Parkinson's Disease (PD). This review examines butyrate's origins, functions, and mechanisms in the gut, its impact on the gut-brain axis, and its relevance in both \"brain-first\" and \"gut-first\" PD models. We also explore the effects of butyrate supplementation in animal models and human clinical studies, highlighting its promise as a therapeutic agent for PD. The understanding of butyrate as a versatile metabolite may pave the way for innovative strategies to prevent or manage PD, stressing the need for integrated approaches targeting both the nervous and gastrointestinal systems.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293009","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}
{"title":"Chemokine CCL2 Mediates Neuroglial Crosstalk and Drives Chronic Pain Pathogenesis.","authors":"Junyu Lu, Yunxin Shi, Yongkang Li, Ziyi Niu, Shengxi Wu, Ceng Luo, Rou-Gang Xie","doi":"10.1007/s12264-025-01519-9","DOIUrl":"https://doi.org/10.1007/s12264-025-01519-9","url":null,"abstract":"<p><p>Chronic pain, frequently comorbid with neuropsychiatric disorders, significantly impairs patients' quality of life and functional capacity. Accumulating evidence implicates the chemokine CCL2 and its receptor CCR2 as key players in chronic pain pathogenesis. This review examines the regulatory mechanisms of the CCL2/CCR2 axis in chronic pain processing at three hierarchical levels: (1) Peripheral Sensitization: CCL2/CCR2 modulates TRPV1, Nav1.8, and HCN2 channels to increase neuronal excitability and CGRP signaling and calcium-dependent exocytosis in peripheral nociceptors to transmit pain. (2) Spinal Cord Central Sensitization: CCL2/CCR2 contributes to NMDAR-dependent plasticity, glial activation, GABAergic disinhibition, and opioid receptor desensitization. (3) Supraspinal Central Networks: CCL2/CCR2 signaling axis mediates the comorbidity mechanisms of pain with anxiety and cognitive impairment within brain regions, including the ACC, CeA, NAc, and hippocampus, and it also increases pain sensitization through the descending facilitation system. Current CCL2/CCR2-targeted therapeutic strategies and their development status are discussed, highlighting novel avenues for chronic pain management.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286713","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}
Chunyi Cui, Xiaofeng Dou, Peili Cen, Chentao Jin, Jing Wang, Jiaqi Niu, Chenxi Xue, Mei Tian, Hong Zhang, Yan Zhong
{"title":"PET Molecular Imaging of the Endocannabinoid System in Psychiatric Disorders.","authors":"Chunyi Cui, Xiaofeng Dou, Peili Cen, Chentao Jin, Jing Wang, Jiaqi Niu, Chenxi Xue, Mei Tian, Hong Zhang, Yan Zhong","doi":"10.1007/s12264-025-01515-z","DOIUrl":"https://doi.org/10.1007/s12264-025-01515-z","url":null,"abstract":"<p><p>Psychiatric disorders have emerged as significant contributors to the global burden of disease in recent decades. The endocannabinoid system (ECS) influences a range of physiological and pathophysiological processes, including nociception, cognition, appetite, memory, and behavior, serving as a crucial mediator in psychiatric disorders. Imaging the ECS provides valuable insights into the pathophysiological mechanisms underlying psychiatric disorders and enhances clinical management strategies. As an advanced noninvasive molecular imaging modality, positron emission tomography (PET) enables the in vivo exploration of biological processes at the cellular and molecular levels. Recent advancements have led to the development of numerous PET tracers that target various components of the ECS, offering opportunities to visualize, characterize, and quantify ECS activity in psychiatric disorders in vivo. In this review, we summarize the existing PET tracers for ECS imaging and discuss their applications in diverse psychiatric conditions, including cannabis use disorder, alcohol use disorder, post-traumatic stress disorder, schizophrenia, and eating disorders.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286703","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}
Lu Ding, Xinyue Li, YaQin Guo, Feng-Quan Zhou, David Y B Deng
{"title":"Complement C3a Suppresses Spinal Cord Neural Stem Cell Activation by Inhibiting UCHL1 via the NF-κB p65/Nrf2 Pathway.","authors":"Lu Ding, Xinyue Li, YaQin Guo, Feng-Quan Zhou, David Y B Deng","doi":"10.1007/s12264-025-01488-z","DOIUrl":"https://doi.org/10.1007/s12264-025-01488-z","url":null,"abstract":"<p><p>Activation of spinal cord neural stem cells (NSCs) and subsequent neurogenesis holds a promising alternative for spinal cord injury (SCI) repair. Our previous study demonstrated that complement C3a, derived from reactive astrocytes, inhibits NSC proliferation by suppressing protein aggregate clearance through the deubiquitinating enzyme ubiquitin carboxy-terminal hydrolase L1 (UCHL1)-proteasome system post-SCI. However, the potential molecular mechanism by which C3a modulates NSC activation via this pathway remains unclear. Here, we revealed that C3a/C3a receptor (C3aR) signaling activated NF-κB p65, which in turn inhibited Nrf2 activity and UCHL1 expression, resulting in diminished proteasome activity and the accumulation of protein aggregates, and ultimately impaired NSC activation. Both knockdown of NF-κB p65 and Nrf2 upregulation restored UCHL1 expression and proteasome activity in vitro, promoting NSC activation by enhancing protein aggregate clearance. Mechanistically, we found that NF-κB p65 regulated Nrf2 activity through a dual mechanism: (1) promoting Keap1-dependent ubiquitination and proteasome degradation of Nrf2; (2) inhibiting protein kinase C-mediated Nrf2 phosphorylation and nuclear translocation. Using the dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) analysis, we further identified UCHL1 as a direct transcriptional target of Nrf2. Importantly, in vivo experiments using SCI mice confirmed that either C3aR blockade, NF-κB p65 knockdown, or Nrf2 overexpression could rescue SCI-induced UCHL1 downregulation. Together, this study uncovers the C3a-NF-κB p65-Nrf2-UCHL1-proteasome axis as a critical regulator of NSC activation after SCI. This may provide novel molecular targets and intervention strategies for SCI repair.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225496","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}
Neuroscience bulletinPub Date : 2025-10-01Epub Date: 2025-06-25DOI: 10.1007/s12264-025-01439-8
Tingting Liu, Haojie Wu, Jianshe Wei
{"title":"Bridging the Gap: The Neuro-immune Axis as a Key Player in Neurodegenerative Disorders.","authors":"Tingting Liu, Haojie Wu, Jianshe Wei","doi":"10.1007/s12264-025-01439-8","DOIUrl":"10.1007/s12264-025-01439-8","url":null,"abstract":"<p><p>Neurodegenerative diseases encompass a diverse array of disorders that have a profoundly detrimental impact on human health, characterized by their intricate and multifaceted pathogenesis. In the recent past, a growing body of scientific research has begun to shed light on the critical involvement of the neuro-immune axis in the onset and advancement of these debilitating conditions. This comprehensive review article delves into the intricate composition of the neuro-immune axis, elucidating the complex mechanisms through which it exerts its influence in the context of neurodegenerative diseases. Furthermore, it explores the potential therapeutic applications of targeting the neuro-immune axis for the management and treatment of these diseases. This extensive examination aims to offer new perspectives and innovative strategies that could pave the way for more effective treatments for neurodegenerative diseases, thereby providing hope for those afflicted by these challenging conditions.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":"1867-1887"},"PeriodicalIF":5.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485210","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}
Neuroscience bulletinPub Date : 2025-10-01Epub Date: 2025-07-21DOI: 10.1007/s12264-025-01458-5
Jiamin Bu, Guangwei Xu, Yifeng Zhou
{"title":"Parvalbumin and Somatostatin Neurons in the Thalamic Reticular Nucleus Modulate Visual Information Processing in V1 of Mouse.","authors":"Jiamin Bu, Guangwei Xu, Yifeng Zhou","doi":"10.1007/s12264-025-01458-5","DOIUrl":"10.1007/s12264-025-01458-5","url":null,"abstract":"<p><p>The thalamic reticular nucleus (TRN) plays a crucial role in regulating sensory encoding, even at the earliest stages of visual processing, as evidenced by numerous studies. Orientation selectivity, a vital neural response, is essential for detecting objects through edge perception. Here, we demonstrate that somatostatin (SOM)-expressing and parvalbumin (PV)-expressing neurons in the TRN project to the dorsal lateral geniculate nucleus and modulate orientation selectivity and the capacity for visual information processing in the primary visual cortex (V1). These findings show that SOM-positive and PV-positive neurons in the TRN are powerful modulators of visual information encoding in V1, revealing a novel role for this thalamic nucleus in influencing visual processing.</p>","PeriodicalId":19314,"journal":{"name":"Neuroscience bulletin","volume":" ","pages":"1824-1842"},"PeriodicalIF":5.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675374","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}