Molecular and Cellular Neuroscience最新文献

The glymphatic and meningeal lymphatic systems may converge, connecting traumatic brain injury progression with chronic traumatic encephalopathy onset 淋巴系统和脑膜淋巴系统可能会聚，将创伤性脑损伤的进展与慢性创伤性脑病的发病联系起来

IF 2.6 3区医学

Molecular and Cellular Neuroscience Pub Date : 2025-07-23 DOI: 10.1016/j.mcn.2025.104031

Randy Bent Barker , Eda Karakaya , Didem Baran , Adviye Ergul , Kaan Yagmurlu , Mehmet Albayram , Onder Albayram

{"title":"The glymphatic and meningeal lymphatic systems may converge, connecting traumatic brain injury progression with chronic traumatic encephalopathy onset","authors":"Randy Bent Barker , Eda Karakaya , Didem Baran , Adviye Ergul , Kaan Yagmurlu , Mehmet Albayram , Onder Albayram","doi":"10.1016/j.mcn.2025.104031","DOIUrl":"10.1016/j.mcn.2025.104031","url":null,"abstract":"<div><div>Chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease marked by perivascular deposition of hyperphosphorylated tau (P-tau), is strongly linked to repetitive concussive traumatic brain injuries (TBIs). Emerging evidence implicates disruptions in the clearance of interstitial fluid (ISF) and cerebrospinal fluid (CSF) from the brain—specifically within the glymphatic and meningeal lymphatic systems—as a pivotal driver of disease onset and progression. TBI disrupts glymphatic ISF–CSF exchange, compromising the clearance of pathogenic proteins—including P-tau, TDP-43, and inflammatory mediators—while promoting perivascular accumulation and neuroinflammation. Simultaneously, meningeal lymphatic dysfunction impedes CSF drainage and sustains neuroimmune activation, further amplifying glymphatic failure. Developmental trajectories of these systems suggest age-dependent susceptibilities to injury, potentially shaping both acute outcomes and long-term neurodegenerative risk. Species-specific differences between rodents and humans in brain fluid clearance pathways add translational complexity, emphasizing the need for refined models. This review reconceptualizes CTE as a disorder driven by disrupted brain fluid clearance, highlighting the convergent roles of glymphatic and meningeal lymphatic dysfunction in linking TBI to chronic neurodegeneration and identifying therapeutic targets to restore clearance and resilience.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"134 ","pages":"Article 104031"},"PeriodicalIF":2.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Ubiquitous calpastatin overexpression in brain-injured mice attenuates motor and cognitive behavioral deficits without overt neuroprotection. 脑损伤小鼠中普遍存在的钙pastatin过表达可减轻运动和认知行为缺陷，但没有明显的神经保护作用。

IF 2.6 3区医学

Molecular and Cellular Neuroscience Pub Date : 2025-07-22 DOI: 10.1016/j.mcn.2025.104032

Kathleen M Schoch, Dominic N Nthenge-Ngumbau, Jennifer M Brelsfoard, Gregory S Hawk, Kathryn E Saatman

{"title":"Ubiquitous calpastatin overexpression in brain-injured mice attenuates motor and cognitive behavioral deficits without overt neuroprotection.","authors":"Kathleen M Schoch, Dominic N Nthenge-Ngumbau, Jennifer M Brelsfoard, Gregory S Hawk, Kathryn E Saatman","doi":"10.1016/j.mcn.2025.104032","DOIUrl":"https://doi.org/10.1016/j.mcn.2025.104032","url":null,"abstract":"<p><p>Calpains are a family of calcium-dependent cysteine proteases that are activated within the brain minutes after a traumatic brain injury (TBI). Sustained calpain activation contributes to the secondary injury cascade of TBI and has been linked to neuronal and axonal degeneration and impairment of neurological function. Calpastatin is an endogenous protein encoded by the CAST gene which serves as a potent and highly selective inhibitor of calpains. This study investigates the potential of overexpressing human calpastatin (hCAST) via the ubiquitous prion protein promoter in a mouse model to alleviate TBI-induced brain damage and neurobehavioral dysfunction. Transgenic mice overexpressing hCAST and wildtype controls received a controlled cortical impact to induce contusive TBI or a sham injury. Overexpression of calpastatin significantly attenuated motor deficits over the first week in brain-injured mice. Visuospatial learning ability assessed in a Morris water maze on days 6 through 9 and novel object recognition on day 10 were impaired following TBI in wildtype mice. Both learning and memory function were improved in brain-injured hCAST overexpressing mice compared to wildtype mice. At 10 days post-injury brains were evaluated for cortical tissue damage and hippocampal neuron death. Analysis of Nissl-stained brain sections revealed no significant difference in the size of the cortical contusion between hCAST and wildtype animals. Similarly, hippocampal neurodegeneration associated with TBI was not modulated by hCAST overexpression. These findings demonstrate that inhibition of calpains aids in restoration of neurobehavioral function following TBI without protecting against cortical or hippocampal neuron death.</p>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":" ","pages":"104032"},"PeriodicalIF":2.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

DAPK1 induces motor neuron apoptosis in hSOD1G93A-linked amyotrophic lateral sclerosis via regulating the Xiap/JNK pathway DAPK1通过调节Xiap/JNK通路诱导hsod1g93a相关肌萎缩性侧索硬化运动神经元凋亡

IF 2.6 3区医学

Molecular and Cellular Neuroscience Pub Date : 2025-07-14 DOI: 10.1016/j.mcn.2025.104029

Xiaoli Su , Xingli Tan , Ying Wang , Weiwei Liang , Di Wang , Di Huo , Hongyong Wang , Yan Qi , Wenmo Zhang , Ling Han , Dongmei Zhang , Ming Wang , Jing Xu , Honglin Feng

{"title":"DAPK1 induces motor neuron apoptosis in hSOD1G93A-linked amyotrophic lateral sclerosis via regulating the Xiap/JNK pathway","authors":"Xiaoli Su , Xingli Tan , Ying Wang , Weiwei Liang , Di Wang , Di Huo , Hongyong Wang , Yan Qi , Wenmo Zhang , Ling Han , Dongmei Zhang , Ming Wang , Jing Xu , Honglin Feng","doi":"10.1016/j.mcn.2025.104029","DOIUrl":"10.1016/j.mcn.2025.104029","url":null,"abstract":"<div><div>Death-associated protein kinase 1 (DAPK1) is critically involved in regulating cell death in various neurodegenerative disorders. However, the role of DAPK1 in the pathogenesis of amyotrophic lateral sclerosis (ALS) remains unclear. Here, we found that the expression of DAPK1 significantly increased in ALS, showing a negative correlation with miR-501-3p. Upregulating DAPK1 led to an increase in motor neuron apoptosis by inhibiting Xiap. Conversely, silencing of DAPK1 protected motor neurons against hSOD1<sup>G93A</sup>-induced apoptosis by activating Xiap. Furthermore, we demonstrate that the neuroprotective impact of DAPK1-knockdown was inhibited by Embelin, an inhibitor of Xiap. These results suggest that modulating the DAPK1/Xiap signaling cascade protects motor neurons from apoptosis, indicating its potential as a therapeutic target in ALS. Significantly, these findings offer new directions for treatment options for ALS patients.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"134 ","pages":"Article 104029"},"PeriodicalIF":2.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144633328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Neuroprotective effect of the peroxisome proliferator-activated receptor γ agonist lobeglitazone following intracerebral hemorrhage in rats. 过氧化物酶体增殖物激活受体γ激动剂洛贝列酮对脑出血大鼠的神经保护作用。

IF 2.6 3区医学

Molecular and Cellular Neuroscience Pub Date : 2025-07-10 DOI: 10.1016/j.mcn.2025.104030

Tae Jung Kim, Young-Ju Kim, Soo-Hyun Park, Youngjoon Kim, Sang-Bae Ko

{"title":"Neuroprotective effect of the peroxisome proliferator-activated receptor γ agonist lobeglitazone following intracerebral hemorrhage in rats.","authors":"Tae Jung Kim, Young-Ju Kim, Soo-Hyun Park, Youngjoon Kim, Sang-Bae Ko","doi":"10.1016/j.mcn.2025.104030","DOIUrl":"https://doi.org/10.1016/j.mcn.2025.104030","url":null,"abstract":"<p><p>Lobeglitazone, an oral antidiabetic medication, acts as a peroxisome proliferator-activated receptor γ (PPARγ) agonist and demonstrates neuroprotective effects. This study investigated beneficial effects and mechanisms of lobeglitazone treatment in an experimental intracerebral hemorrhage (ICH) rat model. ICH was induced in the left striatum of Sprague-Dawley rats by administration of 0.6 units of collagenase type IV. Rats with ICH were assigned randomly to three treatment groups: (1) control group, (2) lobeglitazone 2 mg/kg, and (3) lobeglitazone 4 mg/kg (N = 6, in each group). Medications were administered orally for 3 days following ICH. Outcomes were measured based on brain edema on the third day after ICH. Behavioral outcomes were evaluated on days 1, 3, 6, and 13 following ICH utilizing the modified neurological severity score (mNSS). On the third day after ICH, inflammatory cytokines were evaluated using western blotting, and inflammatory cells were examined through immunohistochemistry. Administration of lobeglitazone at a dosage of 4 mg/kg reduced brain edema significantly (15 %) in comparison to the control and 2 mg/kg (7 %) groups. Moreover, lobeglitazone administration at a dosage of 4 mg/kg suppressed infiltration of macrophages and neutrophils in perihematomal areas. Expression of several inflammatory cytokines, including interleukin-1 beta (IL-1b), extracellular signal-regulated kinase (ERK), and cyclooxygenase-2 (COX2) were also reduced. Regarding functional outcomes, a high dose of lobeglitazone (4 mg/kg) improved the mNSS significantly on days 3 and 13 after ICH. The results suggest that lobeglitazone, a PPARγ agonist, has potential neuroprotective effects on ICH by modulating brain edema and brain inflammation via IL-1β-ERK-COX-2 pathway inhibition.</p>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":" ","pages":"104030"},"PeriodicalIF":2.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Sex-specific neuroprotection: Does BDNF shield girls from autism? 性别特异性神经保护：BDNF能保护女孩远离自闭症吗？

IF 2.6 3区医学

Molecular and Cellular Neuroscience Pub Date : 2025-07-08 DOI: 10.1016/j.mcn.2025.104028

Takshashila Wankhade, Nayan Thakre, Manasi Tadas, Raj Katariya, Milind Umekar, Nandkishor Kotagale, Brijesh Taksande

{"title":"Sex-specific neuroprotection: Does BDNF shield girls from autism?","authors":"Takshashila Wankhade, Nayan Thakre, Manasi Tadas, Raj Katariya, Milind Umekar, Nandkishor Kotagale, Brijesh Taksande","doi":"10.1016/j.mcn.2025.104028","DOIUrl":"https://doi.org/10.1016/j.mcn.2025.104028","url":null,"abstract":"<p><p>Autism Spectrum Disorder (ASD) exhibits a clear male bias, with males being approximately four times more likely to be affected than females. This difference has sparked curiosity about possible neurological elements that provide protection to females. One such neurological element that has shown promise is brain-derived neurotrophic factor (BDNF), essential for neuronal development, synaptic plasticity, and neuroprotection. ASD may be less common in females due to increased BDNF levels, which may be influenced by sex-specific epigenetic control and estrogen hormone. Research studies indicate that increased baseline BDNF in females promotes neurodevelopmental resilience and mitigates the environmental and genetic risk factors linked to ASD. Also, this protective impact may be enhanced by the regulatory function of estrogen in BDNF expression and the interaction of BDNF with X-linked genes. The processes by which BDNF contributes to sex differences are still not well understood despite strong evidence. Interpreting results is made more difficult by the variability of ASD symptoms and variations in study methodologies. In addition to that, it is yet unknown whether increased BDNF levels represent compensatory processes or actually provide protection. Longitudinal studies that monitor BDNF expression across developmental stages and look at sex-specific treatment approaches that target BDNF pathways should be the main focus of future research. Thus, a thorough understanding of how BDNF prevents sex differences in ASD may pave the way for innovative strategies destined to diminish the risk of ASD. In this milieu, this review explores the current research, highlighting the complex relationship between sex differences, BDNF, and the incidence of ASD.</p>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":" ","pages":"104028"},"PeriodicalIF":2.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

A critical role for the fascin family of actin bundling proteins in axon development, brain wiring and function 肌动蛋白束蛋白家族在轴突发育、大脑布线和功能中的关键作用

IF 2.6 3区医学

Molecular and Cellular Neuroscience Pub Date : 2025-06-17 DOI: 10.1016/j.mcn.2025.104027

Katherine R. Hardin , Arjolyn B. Penas , Shuristeen Joubert , Changtian Ye , Kenneth R. Myers , James Q. Zheng

{"title":"A critical role for the fascin family of actin bundling proteins in axon development, brain wiring and function","authors":"Katherine R. Hardin , Arjolyn B. Penas , Shuristeen Joubert , Changtian Ye , Kenneth R. Myers , James Q. Zheng","doi":"10.1016/j.mcn.2025.104027","DOIUrl":"10.1016/j.mcn.2025.104027","url":null,"abstract":"<div><div>Actin-based cell motility drives many neurodevelopmental events including guided axonal growth. Fascin is a major family of F-actin bundling proteins, but its role in axon development <em>in vivo</em> and brain wiring remains unclear. Here, we report that fascin is required for axon development, brain wiring and function. We show that fascin is enriched in the motile filopodia of axonal growth cones and its inhibition impairs axonal extension and branching of hippocampal neurons in culture. We next provide evidence that fascin is essential for axon development and brain wiring <em>in vivo</em> using <em>Drosophila melanogaster</em> as a model. <em>Drosophila</em> expresses a single ortholog of mammalian fascin called Singed (Sn), which is expressed in the mushroom body (MB) of the central nervous system. Loss of Sn causes severe MB disruption, marked by α- and β-lobe defects indicative of altered axonal guidance. Sn-null flies also exhibit defective sensorimotor behaviors as assessed by the negative geotaxis assay. MB-specific expression of Sn in Sn-null flies rescues MB structure and sensorimotor deficits, indicating that Sn functions autonomously in MB neurons. Together, our data from primary neuronal culture and <em>in vivo</em> models highlight a critical role for fascin in brain development and function.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"134 ","pages":"Article 104027"},"PeriodicalIF":2.6,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Multiple models of TBI in Drosophila yield common and unique genetic, physiological, behavioral outcomes 多种模型的TBI在果蝇产生共同的和独特的遗传，生理，行为结果

IF 2.6 3区医学

Molecular and Cellular Neuroscience Pub Date : 2025-06-08 DOI: 10.1016/j.mcn.2025.104024

Seanna E. Kelly , Rebecca Delventhal , Annika F. Barber

{"title":"Multiple models of TBI in Drosophila yield common and unique genetic, physiological, behavioral outcomes","authors":"Seanna E. Kelly , Rebecca Delventhal , Annika F. Barber","doi":"10.1016/j.mcn.2025.104024","DOIUrl":"10.1016/j.mcn.2025.104024","url":null,"abstract":"<div><div>Traumatic brain injury is a significant public health problem, but the complex pathology of TBI has posed a barrier to a molecular understanding of the root causes of post-TBI sequelae. Fruit fly models of TBI offer opportunities to conduct high throughput screens for genes affecting multiple outcomes of TBI. This review provides a primer on fly traumatic injury paradigms, a summary of findings made in fly TBI models, and recommendations for future areas of TBI research amenable to the fly model. Using the whole-animal and head-specific TBI paradigms available in Drosophila, researchers have identified changes in acute mortality and median lifespan, reduction in locomotor function, immune activation, remodeling of metabolic functions and sleep, and acceleration of neurodegenerative phenotypes. Fly TBI models also show effects of age, diet, and sex on injury outcomes. Drosophila genetic tools offer unique advantages for high throughput screening, and fly screens have identified genes that affect acute mortality after injury. Further standardization of fly TBI paradigms will advance the field and allow discovery of genes and biochemical pathways that affect TBI outcomes across species and accelerate the development of evidence-based treatments for TBI survivors.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"134 ","pages":"Article 104024"},"PeriodicalIF":2.6,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144263621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Rethinking Parkinson's: The role of proteostasis networks and autophagy in disease progression 重新思考帕金森病：蛋白质平衡网络和自噬在疾病进展中的作用。

IF 2.6 3区医学

Molecular and Cellular Neuroscience Pub Date : 2025-06-07 DOI: 10.1016/j.mcn.2025.104023

Akhil Sharma, Ashi Mannan, Thakur Gurjeet Singh

{"title":"Rethinking Parkinson's: The role of proteostasis networks and autophagy in disease progression","authors":"Akhil Sharma, Ashi Mannan, Thakur Gurjeet Singh","doi":"10.1016/j.mcn.2025.104023","DOIUrl":"10.1016/j.mcn.2025.104023","url":null,"abstract":"<div><div>Protein dyshomeostasis is identified as the hallmark of many age-related NDDs including Parkinson's disease (PD). PD is a progressive neurodegenerative disorder (NDD) characterized by the accumulation of misfolded proteins, particularly α-synuclein (α-syn) leading to formation of Lewy bodies and cause degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc). Disruption of the cell's normal protein balance, which occurs when cells experience stress, plays a key role in causing the formation of harmful protein clumps. Functional proteostasis relies on coordinated mechanisms involving posttranslational modifications (PTMs), molecular chaperones, the unfolded protein response (UPR), the ubiquitin-proteasome system (UPS), and the autophagy-lysosome pathway (ALP). These networks maintain proper synthesis, folding, confirmation and degradation of protein such as α-syn protein in PD. These approaches include enhancing lysosomal function, promoting autophagy and modulating the unfolded protein response. Understanding the complex interactions between these pathways is essential for developing effective treatments. This review synthesizes current knowledge of various genes and molecular mechanisms underlying proteostasis disruption in PD and evaluates emerging therapeutic strategies that target multiple genes and pathways simultaneously. The finding highlights the potential of integrated approaches to restore protein homeostasis and prevent neurodegeneration, offering new directions for PD treatment development.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"134 ","pages":"Article 104023"},"PeriodicalIF":2.6,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Apelin-13 can regulate adipose-derived mesenchymal stem cells to improve traumatic brain injury Apelin-13可调节脂肪源性间充质干细胞改善外伤性脑损伤。

IF 2.6 3区医学

Molecular and Cellular Neuroscience Pub Date : 2025-06-06 DOI: 10.1016/j.mcn.2025.104016

Min Huang , Yong Zhang , Yanyang Shen, Yiqin Xu, Xuehong Liu

引用次数: 0

Regulation of hippocampal excitatory synapse development by the adhesion G-protein coupled receptor brain-specific angiogenesis inhibitor 2 (BAI2/ADGRB2) 粘附g蛋白偶联受体脑特异性血管生成抑制剂2 （BAI2/ADGRB2）对海马兴奋性突触发育的调控

IF 2.6 3区医学

Molecular and Cellular Neuroscience Pub Date : 2025-05-30 DOI: 10.1016/j.mcn.2025.104015

Christina M. Meyer, Olga Vafaeva, Henry Low, David J. Speca, Elva Díaz

{"title":"Regulation of hippocampal excitatory synapse development by the adhesion G-protein coupled receptor brain-specific angiogenesis inhibitor 2 (BAI2/ADGRB2)","authors":"Christina M. Meyer, Olga Vafaeva, Henry Low, David J. Speca, Elva Díaz","doi":"10.1016/j.mcn.2025.104015","DOIUrl":"10.1016/j.mcn.2025.104015","url":null,"abstract":"<div><div>Glutamatergic synapses and their associated dendritic spines are critical information processing sites within the brain. Proper development of these specialized cellular junctions is important for normal brain functionality. Synaptic adhesion G protein-coupled receptors (aGPCRs) have been identified as regulators of synapse development and function. While two members of the Brain-specific angiogenesis inhibitor (BAI/ADGRB) subfamily of synaptic aGPCRs, BAI1/ADGRB1 and BAI3/ADGRB3, have been found to mediate synapse and spine formation, BAI2/ADGRB2 function remains uncharacterized at the synapse. Here, we show that endogenous ADGRB2 is expressed throughout the nervous system with prominent expression in synapse dense regions of the hippocampus. In dissociated hippocampal cultures, ADGRB2 is highly enriched at large postsynaptic sites, defined by the size of the postsynaptic scaffold PSD95. Loss of ADGRB2 negatively impacts glutamatergic synapses across development in dissociated hippocampal cultures. In contrast, GABAergic synapse density is unchanged. Furthermore, ADGRB2 deficient neurons have significant alterations in spine morphology with decreased density of mature PSD95-containing mushroom-shaped spines compared with wild-type neurons. Interestingly, no major alterations in dendritic complexity were observed in ADGRB2 deficient neurons, in contrast to previous results for the other BAIs/ADGRBs. The reduction in mature mushroom-shaped spines is commensurate with a reduction in spine volume and head diameter. Altogether, these results demonstrate that the aGPCR ADGRB2 is an important regulator of glutamatergic synapse and PSD95-associated spine development in cultured hippocampal neurons. These results expand the knowledge of the BAI/ADGRB subfamily of aGPCRs in mediating excitatory synapse and spine development and highlight differences unique to ADGRB2.</div></div>","PeriodicalId":18739,"journal":{"name":"Molecular and Cellular Neuroscience","volume":"134 ","pages":"Article 104015"},"PeriodicalIF":2.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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