Molecular Brain最新文献

Integrated molecular data analysis confirms PDK1 as a candidate risk factor in ALS pathophysiology. 综合分子数据分析证实PDK1是ALS病理生理的一个候选危险因素。

IF 2.9 3区医学

Molecular Brain Pub Date : 2025-10-01 DOI: 10.1186/s13041-025-01248-0

Yuqian Liu, Ruiyun Guo, Ni Wang, Yue Yang, Jialu Li, Danyang Jing, Ruoyan Cui, Runchao Ma, Jun Ma

{"title":"Integrated molecular data analysis confirms PDK1 as a candidate risk factor in ALS pathophysiology.","authors":"Yuqian Liu, Ruiyun Guo, Ni Wang, Yue Yang, Jialu Li, Danyang Jing, Ruoyan Cui, Runchao Ma, Jun Ma","doi":"10.1186/s13041-025-01248-0","DOIUrl":"https://doi.org/10.1186/s13041-025-01248-0","url":null,"abstract":"Combining cellular, animal, and MR analyses from three independent cohorts, we identified PDK1 as a consistent risk factor for ALS development, highlighting its potential as a therapeutic target. To further elucidate PDK1's pathogenic mechanisms, we conducted transcriptomic profiling. Samples were stratified into PDK1 high- and low-expression groups. GO and KEGG analyses demonstrated that upregulated DEGs were enriched in pathways involving β-CATENIN, cell adhesion and Ribosome, suggesting a potential role for WNT/β-catenin signaling activation in ALS pathogenesis. To further validate the consistent risk association of PDK1 with ALS across multiple datasets, we utilized 4-month-old SOD1G93A transgenic mice, 4-month-old C9orf72 transgenic mice, and SOD1-overexpressing HEK293T cells. Significant upregulation of PDK1 mRNA was observed in all models, and a significant increase in protein abundance was found in SOD1G93A. This provides strong experimental evidence for the results of the MR study. These results indicate that PDK1 may affect the pathogenesis of amyotrophic lateral sclerosis through genetic variations and transcriptional dysregulation, and may play an important role in the occurrence and development of the disease.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"18 1","pages":"76"},"PeriodicalIF":2.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206834","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

Microglia-astrocyte crosstalk following ischemic stroke. 缺血性中风后小胶质细胞-星形胶质细胞串扰。

IF 2.9 3区医学

Molecular Brain Pub Date : 2025-10-01 DOI: 10.1186/s13041-025-01244-4

Shangsong Yang, Yuxiong Chen, Jialin Tang, Yicheng Cui, Wei Wei, Zhongnan Hao, Zhipeng Xiao, Yongli Pan, Qinyuan Tian, Wenqiang Xin, Meihua Li

引用次数: 0

Identification of VGLUT3-expressing LTMRs-recruited spinal circuits for itch inhibition. 鉴定表达vglut3的ltmr募集脊髓回路对瘙痒的抑制作用。

IF 2.9 3区医学

Molecular Brain Pub Date : 2025-09-30 DOI: 10.1186/s13041-025-01245-3

Xiaojing Su, Liangbiao Wang, Xiaoqing Liu, Yan Zhang

{"title":"Identification of VGLUT3-expressing LTMRs-recruited spinal circuits for itch inhibition.","authors":"Xiaojing Su, Liangbiao Wang, Xiaoqing Liu, Yan Zhang","doi":"10.1186/s13041-025-01245-3","DOIUrl":"10.1186/s13041-025-01245-3","url":null,"abstract":"Itch is a common symptom among patients suffering dermatological and systemic diseases, yet effective clinical treatments are currently lacking. Previous research has suggested that vesicular glutamate transporter 3 (VGLUT3)-lineage sensory neurons may play a role in inhibiting itch, but the circuit mechanisms within the spinal cord remain unclear. In this study, we employed optogenetic techniques to activate VGLUT3-lineage sensory afferents in mice and observed a significant reduction in scratching behaviors elicited by both pruritogens and mechanical stimuli. Moreover, aversive component of chemical itch assessed by conditioned place aversion (CPA) was abrogated. Viral tracing combined with electrophysiological recordings revealed synaptic connections between VGLUT3+ sensory neurons and spinal dynorphin (SCDYN) /neuropeptide Y-expressing (SCNPY) neurons. Further pharmacological studies indicated that intrathecal injection of antagonists of neuropeptide Y1 receptor and kappa opioid receptor (KOR) separately diminished VGLUT3+ neurons-mediated inhibitory effects on mechanical and chemical itch, respectively. In summary, our findings suggest that VGLUT3+ sensory neurons participate in itch regulation through interactions with two classes of inhibitory neurons in the spinal cord, shedding light on potential therapeutic targets for distinct forms of itch management.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"18 1","pages":"74"},"PeriodicalIF":2.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Analgesic effects of transcutaneous auricular vagus nerve stimulation on partial sciatic nerve ligation-induced neuropathic pain in mice via serotonergic pathways. 经皮耳迷走神经刺激经5 -羟色胺能通路对小鼠部分坐骨神经结扎所致神经性疼痛的镇痛作用。

IF 2.9 3区医学

Molecular Brain Pub Date : 2025-09-26 DOI: 10.1186/s13041-025-01246-2

Hyunjin Shin, Seunghwan Choi, Geehoon Chung, Sun Kwang Kim

{"title":"Analgesic effects of transcutaneous auricular vagus nerve stimulation on partial sciatic nerve ligation-induced neuropathic pain in mice via serotonergic pathways.","authors":"Hyunjin Shin, Seunghwan Choi, Geehoon Chung, Sun Kwang Kim","doi":"10.1186/s13041-025-01246-2","DOIUrl":"10.1186/s13041-025-01246-2","url":null,"abstract":"Current treatments for neuropathic pain often provide limited relief and are associated with significant side effects. Transcutaneous auricular vagus nerve stimulation (taVNS) shows promise as a non-pharmacological analgesic approach; however, its optimal therapeutic configuration and underlying brain mechanisms remain incompletely understood. This study investigated the analgesic effects of taVNS on neuropathic pain in a mouse model induced by partial sciatic nerve ligation (PSL), exploring mechanisms and optimizing configurations. PSL-induced neuropathic pain in mice, characterized by mechanical allodynia, was significantly alleviated by taVNS. The most robust analgesic effects were observed with multiple bilateral taVNS sessions, administered once daily for three consecutive days, with effects persisting for at least 48 h post-stimulation. Immunohistochemical analysis of c-Fos expression revealed that taVNS increased neural activity in the dorsal raphe nucleus (DRN), a key source of serotonin, while simultaneously reducing activity in the central amygdala (CeA), a region critical for pain processing and affective responses. Further experiments demonstrated that the analgesic effects of taVNS were abolished by systemic administration of p-chlorophenylalanine, an inhibitor of serotonin synthesis. These findings underscore the critical role of serotonin signaling in mediating taVNS-induced analgesia for neuropathic pain. The study also highlights the importance of stimulation parameters, identifying a multiple bilateral configuration as particularly effective. Our results suggest that taVNS, potentially acting via the DRN-serotonergic system to modulate limbic structures like the CeA, holds significant potential as a non-pharmacological therapeutic option for managing neuropathic pain.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"18 1","pages":"73"},"PeriodicalIF":2.9,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Comprehensive behavioral phenotyping of male Septin 3-deficient mice reveals task-specific abnormalities. 雄性Septin 3缺陷小鼠的综合行为表型揭示了任务特异性异常。

IF 2.9 3区医学

Molecular Brain Pub Date : 2025-08-22 DOI: 10.1186/s13041-025-01243-5

Natsumi Ageta-Ishihara, Keizo Takao, Tsuyoshi Miyakawa, Makoto Kinoshita

引用次数: 0

Voluntary running improves synaptic degeneration of the anterior cingulate cortex in knee osteoarthritis. 自主跑步改善膝骨关节炎患者前扣带皮质突触变性。

IF 2.9 3区医学

Molecular Brain Pub Date : 2025-08-22 DOI: 10.1186/s13041-025-01207-9

Ryo Miyake, Manabu Yamanaka, Wataru Taniguchi, Naoko Nishio, Yuki Matsuyama, Takeru Ueno, Yuta Kaimochi, Terumasa Nakatsuka, Hiroshi Yamada

{"title":"Voluntary running improves synaptic degeneration of the anterior cingulate cortex in knee osteoarthritis.","authors":"Ryo Miyake, Manabu Yamanaka, Wataru Taniguchi, Naoko Nishio, Yuki Matsuyama, Takeru Ueno, Yuta Kaimochi, Terumasa Nakatsuka, Hiroshi Yamada","doi":"10.1186/s13041-025-01207-9","DOIUrl":"https://doi.org/10.1186/s13041-025-01207-9","url":null,"abstract":"Osteoarthritis of the knee (knee OA) causes chronic pain involving peripheral tissues, the spinal cord, and the brain. Neuropathic pain leads to changes in synaptic plasticity in the anterior cingulate cortex (ACC). However, whether such changes occur in knee OA mice and their association with exercise therapy remains unclear. Therefore, this study investigated these aspects using electrophysiological and behavioral approaches. We found no induction of pre- or post-long-term potentiation (LTP) in the ACC of knee OA mice. Application of ZD7288 and zeta inhibitory peptide (ZIP) reduced the amplitude of evoked excitatory postsynaptic currents, indicating pre-existing changes in synaptic plasticity in the ACC. Microinjection of ZD7288 and ZIP improved pain-escape and anxiety-like behaviors. Voluntary running exercise induced pre- and post-LTP and improved these behaviors in knee OA mice. Exercise therapy for knee OA may alter synaptic plasticity in the ACC, contributing to behavioral improvements.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"18 1","pages":"72"},"PeriodicalIF":2.9,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Generation of a new Slc20a2 knockout mouse line as in vivo model for primary brain calcification. 产生新的Slc20a2敲除小鼠系作为原发性脑钙化的体内模型。

IF 2.9 3区医学

Molecular Brain Pub Date : 2025-08-20 DOI: 10.1186/s13041-025-01240-8

Hisaka Kurita, Hiroki Kitaura, Kazuya Nishii, Tomohiko Masaka, Kazuki Ohuchi, Masatoshi Inden, Akiyoshi Kakita, Masatake Osawa, Isao Hozumi

{"title":"Generation of a new Slc20a2 knockout mouse line as in vivo model for primary brain calcification.","authors":"Hisaka Kurita, Hiroki Kitaura, Kazuya Nishii, Tomohiko Masaka, Kazuki Ohuchi, Masatoshi Inden, Akiyoshi Kakita, Masatake Osawa, Isao Hozumi","doi":"10.1186/s13041-025-01240-8","DOIUrl":"https://doi.org/10.1186/s13041-025-01240-8","url":null,"abstract":"Primary brain calcification (PBC) is a neurodegenerative disease that causes bilateral ectopic calcification in the brain. In this study, using newly generated Slc20a2 knockout (Slc20a2-/-) mice, we establish an in vivo model for PBC. In contrast to heterozygous Slc20a2+/- mice (9/9 animals) showing no obvious abnormalities, the homozygous Slc20a2-/- mice exhibited severe calcification at 11 months of age (5/5 animals). Whilst smaller in size and number, the deposits were also detectable in 5-month-old Slc20a2-/- mice (2/2 animals). By contrast, no obvious alterations were detectable in visceral organs, including the lung, kidney, liver, and spleen. Consistently, in PBC patients, despite the systemic mineral metabolic disturbance, calcification occurs only in a brain restricted manner. Hence, these observations suggest that our mouse model is capable of recapitulating certain aspects of human PBC etiology. In summary, our data suggested the utility of an in vivo PBC mouse model in understanding the pathological mechanisms behind brain calcification, which leads in development of novel therapeutics against PBC.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"18 1","pages":"70"},"PeriodicalIF":2.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12369223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Peripheral substance P induces deficits in hippocampal synaptic plasticity and memory. 外周P物质诱导海马突触可塑性和记忆缺陷。

IF 2.9 3区医学

Molecular Brain Pub Date : 2025-08-16 DOI: 10.1186/s13041-025-01242-6

Sun Yong Kim, Kyeong-No Yoon, Jungeun Ji, Min-Gyun Kim, Seung Ah Choi, Gunhyuk Park, Won-Woo Lee, Jin Ho Chung, Sang Jeong Kim, Joon-Yong An, Dong Hun Lee, Yong-Seok Lee

{"title":"Peripheral substance P induces deficits in hippocampal synaptic plasticity and memory.","authors":"Sun Yong Kim, Kyeong-No Yoon, Jungeun Ji, Min-Gyun Kim, Seung Ah Choi, Gunhyuk Park, Won-Woo Lee, Jin Ho Chung, Sang Jeong Kim, Joon-Yong An, Dong Hun Lee, Yong-Seok Lee","doi":"10.1186/s13041-025-01242-6","DOIUrl":"10.1186/s13041-025-01242-6","url":null,"abstract":"Substance P (SP) is a neuropeptide that functions in both the central and peripheral nervous systems. Although the peripheral actions of SP in regulating inflammatory responses have been extensively investigated, the effects of elevated peripheral SP on hippocampal functions such as spatial learning and memory remains unclear, even though SP can cross the blood-brain barrier. In this study, we found that male mice subcutaneously injected with SP for 14 days exhibited significant deficits in hippocampus-dependent memory, as assessed by the object place recognition and novel object recognition tests. In addition, long-term potentiation (LTP) at the hippocampal CA3-CA1 synapse was reduced in SP-treated mice. Transcriptomic analyses identified 77 differentially expressed genes (DEGs), and enrichment analysis highlighted pathways related to synaptic transmission, learning, and memory. These results suggest a novel skin-brain neuropeptide signaling axis. Targeting peripheral SP or its receptor may provide a therapeutic avenue for cognitive dysfunction associated with peripheral inflammation.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"18 1","pages":"69"},"PeriodicalIF":2.9,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12358064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Neurodegeneration in Parkinson's disease: are we looking at the right spot? 帕金森氏症的神经退化：我们找对地方了吗？

IF 2.9 3区医学

Molecular Brain Pub Date : 2025-08-01 DOI: 10.1186/s13041-025-01218-6

Gabriel S Rocha, Marco Aurelio M Freire, Daniel Falcao, Tiago F Outeiro, Rafael R Lima, Jose Ronaldo Santos

{"title":"Neurodegeneration in Parkinson's disease: are we looking at the right spot?","authors":"Gabriel S Rocha, Marco Aurelio M Freire, Daniel Falcao, Tiago F Outeiro, Rafael R Lima, Jose Ronaldo Santos","doi":"10.1186/s13041-025-01218-6","DOIUrl":"10.1186/s13041-025-01218-6","url":null,"abstract":"Parkinson's disease (PD) is recognized as the fastest-growing neurodegenerative disorder, impacting millions of individuals worldwide. It is primarily characterized by cardinal motor symptoms, including bradykinesia (slowness of movement), tremor, rigidity, and postural instability, which significantly impair the quality of life of those affected. Traditionally, the prevailing hypothesis has attributed these motor symptoms to the degeneration and subsequent loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Currently, emerging research suggests that this neuron-centric view may be overly simplistic and not entirely accurate. In light of this, growing attention has turned to the role of axons within the nigrostriatal pathway-an extensive network connecting the substantia nigra to the striatum, essential for both dopamine transmission and the overall functioning of the motor control by the brain. By directing a focus toward this aspect, in this nano review article we examine why nigrostriatal axons deserve increased attention and should be considered a pivotal target for further therapeutic strategies in PD.","PeriodicalId":18851,"journal":{"name":"Molecular Brain","volume":"18 1","pages":"68"},"PeriodicalIF":2.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12315329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Unraveling the mystery: How autophagy deficiency in dopaminergic neurons drives human Parkinson's disease. 解开谜团：多巴胺能神经元的自噬缺陷如何驱动人类帕金森病。

IF 2.9 3区医学

Molecular Brain Pub Date : 2025-07-24 DOI: 10.1186/s13041-025-01235-5

Sachiko Noda, Nobutaka Hattori

引用次数: 0