CBLN1

更新于：2025-05-07

基本信息

别名

[des-Ser1]-cerebellin、CBLN1、CER

+ [4]

简介

The cerebellin peptide exerts neuromodulatory functions. Directly stimulates norepinephrine release via the adenylate cyclase/PKA-dependent signaling pathway; and indirectly enhances adrenocortical secretion in vivo, through a paracrine mechanism involving medullary catecholamine release (By similarity). Required for synapse integrity and synaptic plasticity. During cerebellar synapse formation, essential for the matching and maintenance of pre- and post-synaptic elements at parallel fiber-Purkinje cell synapses, the establishment of the proper pattern of climbing fiber-Purkinje cell innervation, and induction of long-term depression at parallel fiber-Purkinje cell synapses. Plays a role as a synaptic organizer that acts bidirectionally on both pre- and post-synaptic components. On the one hand induces accumulation of synaptic vesicles in the pre-synaptic part by binding with NRXN1 and in other hand induces clustering of GRID2 and its associated proteins at the post-synaptic site through association of GRID2. NRXN1-CBLN1-GRID2 complex directly induces parallel fiber protrusions that encapsulate spines of Purkinje cells leading to accumulation of GRID2 and synaptic vesicles. Required for CBLN3 export from the endoplasmic reticulum and secretion (By similarity). NRXN1-CBLN1-GRID2 complex mediates the D-Serine-dependent long term depression signals and AMPA receptor endocytosis (PubMed:27418511). Essential for long-term maintenance but not establishment of excitatory synapses (By similarity). Inhibits the formation and function of inhibitory GABAergic synapses in cerebellar Purkinje cells (By similarity).

关联

100 项与 CBLN1 相关的临床结果

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100 项与 CBLN1 相关的转化医学

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0 项与 CBLN1 相关的专利（医药）

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157

项与 CBLN1 相关的文献（医药）

2025-05-01·Experimental Eye Research

Regeneration of retinal ganglion cell-like cells and reconstruction of visual neural circuits in mice with glaucoma

Article

作者: Xu, Lin ; Li, Wei ; Liu, Jianjun ; Wang, He ; Zhang, Zhenhao ; Liu, Ya

Glaucoma is an irreversible blinding eye disease characterized by apoptosis of mature neurons-retinal ganglion cells (RGCs), visual field defect and vision loss. Regeneration of RGCs and reconstruction of the neural connections between the retina and the brain is considered an effective strategy to promote visual restoration in patients with glaucoma. However, there are currently no effective methods for regenerating RGCs to restore vision in clinical practice. Microglia are a type of glial cells that regulate the immune response in the retina and central nervous system (CNS), whether they have pluripotency and be reversed into RGCs remains unclear and challenging. This study revealed that the ectopic expression of multiple genes (Brn3b, Sox2, Cbln1, and NP1, referred to as BSCN) in microglia can promote their conversion into RGC-like cells by microglia fate lineage tracing in vivo. The regenerated RGC-like cells project axons to the distant brain and reconstruct the visual neural circuit, restoring the impaired vision in adult mice with acute glaucoma induced by retinal ischemia-reperfusion (I/R) injury. Furthermore, the regenerated RGC-like cells could survive stably for up to one year, and the same regeneration strategy was performed in older mice with acute glaucoma, which confirmed the effectiveness of the BSCN reprogramming to regenerate RGC-like cells. In summary, we have identified the microglia as a new type of reprogramming seed cells, and four key genes were found to be involved in regenerating RGC-like cells to restore vision. These findings highlight a new strategy of RGC-like cell regeneration and provide a theoretical basis for treatment of glaucoma in the future.

2025-02-01·Nature Neuroscience

Stepwise molecular specification of excitatory synapse diversity onto cerebellar Purkinje cells

Article

作者: Sigoillot, Séverine M ; Delagrange, Marine ; Paul, Maëla A ; Urra Quiroz, Francisco J ; Cheung, Hiu W ; Oriol, Elie ; Selimi, Fekrije ; Hakim, Vincent ; Marti, Léa ; Mailly, Philippe ; Martinelli, David C

Brain function relies on the generation of a large variety of morphologically and functionally diverse, but specific, neuronal synapses. Here we show that, in mice, the initial formation of synapses on cerebellar Purkinje cells involves a presynaptic protein-CBLN1, a member of the C1q protein family-that is secreted by all types of excitatory inputs. The molecular program then evolves only in one of the Purkinje cell inputs, the inferior olivary neurons, with the additional expression of the presynaptic secreted proteins C1QL1, CRTAC1 and LGI2. These molecules work in concert to specify the mature connectivity pattern on the Purkinje cell target. These results show that some inputs actively and gradually specify their synaptic molecular identity, while others rely on the 'original molecular code'. Thus, the molecular specification of excitatory synapses, crucial for proper circuit function, is acquired in a stepwise manner during mouse postnatal development and obeys input-specific rules.

2025-02-01·Brain, Behavior, and Immunity

Do specific myelin autoantibodies and increased cerebral dopamine neurotrophic factor in the context of inflammation predict the diagnosis of attention deficit hyperactivity disorder in medication-free children?

Article

作者: Uçak, Ekrem Furkan ; Ugur, Cüneyt ; Erbasan, Vefa ; Sen, Barıs ; Karatoprak, Serdar ; Can, Ümmügülsüm ; Atas, Abdullah Enes ; Sağlıyan, Gökçeçiçek Arıcı ; Tezcan, Mustafa Esad ; Simsek, Fulya ; Ekici, Fatih ; Güleç, Ahmet

BACKGROUNDThe aim of this study was to investigate the serum levels of anti-myelin basic protein (anti-MBP), anti-myelin oligodentrocyte glycoprotein (anti-MOG), myelin-associated glycoprotein (MAG), high-sensitivity C-reactive protein (hs-CRP), cerebral dopamine neurotrophic factor (CDNF), cerebellin-1, and reelin and their relationships with clinical severity and irritability behaviours in children with attention deficit (AD) hyperactivity disorder (ADHD) and typically developing (TD) healthy controls.METHODSIn this study, 141 children with ADHD between the ages of 8 and 14 years who were medication-free and 135 TD healthy controls were included. The serum levels of anti-MBP, anti-MOG, MAG, CDNF, hs-CRP, cerebellin, and reelin were measured using enzyme-linked immunosorbent assay kits. The Turgay Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-based Screening and Evaluation Scale for Attention Deficit and Disruptive Behavior Disorders-Parent Form (TDSM-IV-O) and the affective reactivity index (ARI) scale were used to assess clinical severity and irritability behaviours in the children.RESULTSThe MAG, CDNF, hs-CRP, reelin, and cerebellin levels were significantly higher in the ADHD group than in the control group, but no significant differences in anti-MBP and anti-MOG levels were found between the groups. Compared with the controls, the patients with ADHD showed significantly higher scores on the ARI self- and parent-report scales. The reelin, hs-CRP, and MAG levels were significantly associated with the TDSM-IV-O AD scores, AD and oppositional defiant (OD) disorder scores and hyperactivity, and OD and conduct disorder scores, respectively. Hs-CRP was significantly associated with anti-MBP and cerebellin levels. In an analysis of covariance, the results were unchanged even after controlling for potential confounders such as age, body mass index, and sex.CONCLUSIONThis study demonstrates that MAG, CDNF, hs-CRP, reelin, and cerebellin levels may play a potential role in the pathogenesis of ADHD.

项与 CBLN1 相关的新闻（医药）

2023-12-05

·生物谷

亲妈鉴定系统开启！Science新发现：怀孕可刺激神经干细胞分化，有利于母亲识别亲生幼崽！

众所周知，怀孕时女性的身体会发生翻天覆地的变化，比如说孕妈妈会感受到体温上升、乳房胀痛、恶心呕吐等。有研究认为妊娠对人类神经结构和功能也会有影响，使母亲大脑的结构和功能发生改变。那些看起来自然而然的母性行为，比如母胎依恋、筑巢行为、对婴儿信号的生理响应以及母婴依恋可能最早在妈妈们的大脑里就做出了改变。英国伦敦弗朗西斯·克里克研究所相关研究团队先前在science杂志发表了研究结果表明怀孕期间荷尔蒙激素会根据对未来行为需求的预期来重塑妈妈育儿回路。详见《母爱是女性本能？science顶刊最新研究表示：为了更好的育儿，怀孕期间荷尔蒙会重塑大脑育儿回路！》这些母性行为是否仅仅建立在母亲对于自己的幼崽身上，如果对于非自己生育的幼崽又是否还会有这些现象呢？针对这个问题，第一眼答案肯是否。但是，对于小动物来说又是如何辨别刚出生的幼崽是不是自己的呢？或许正是由于神经元的改变开启母亲的行为，这些神经上的改变导致了母亲对幼崽更强、更有选择性的反应。近日，来自巴塞尔大学的研究团队在《Science》杂志发表了一篇“Pregnancy-responsive pools of adult neural stem cells for transient neurogenesis in mothers”揭示了怀孕期间成体神经干细胞可触发短暂神经发生，而新生神经元有助于母亲通过嗅觉识别幼鼠, 研究也突出了成体干细胞异质性的生理相关性。图1 https://www.science.org/doi/10.1126/science.abo5199我们知道，根据全能性的不同，可以将细胞分为胚胎干细胞和成体干细胞。成体干细胞在人体内普遍的存在，一般情况下，成体干细胞大多处于休眠状态。长期以来，人们一直认为成年哺乳动物神经系统是非再生组织，即脑内的神经细胞是终生存活的，成年的神经元没有再生能力，当成年个体脑损伤后，失去的神经细胞只能由胶质细胞所填充。近年的研究打破了这一传统的认识。20世纪末期，在神经领域内研究的最重要进展之一就是发现了在成年脑组织内存在具有多向分化潜能的神经干细胞，称为成体神经干细胞（Adult neural stem cells, NSCs），这种细胞具有更自我更新和分裂增殖的能力，可以分化为神经系统大部分类型的细胞，对损伤和疾病具有反应能力。这篇研究认为成体神经干细胞有利于大脑的终身可塑性。在成年小鼠脑室-脑室下区(Ventricular-subventricular zone，V-SVZ)，NSCs是异质的，并根据它的位置不同，可以产生不同亚型的嗅球(OB)中间神经元。图2 嗅球的结构嗅球（olfactory bulb，OB）位于额叶下方，是脊椎动物前脑结构中参与嗅觉的部分，用于感知气味。嗅球分为二个不同的结构：主嗅球（Main olfactory Bulb，MOB）及副嗅球（Accessory olfactory bulb，AOB）。嗅球由内而外可分为颗粒细胞层 (GCL)、二尖瓣细胞层 (MCL)、肾小球层 (GL)等。已知怀孕会引起多个大脑区域的重大结构变化，为母亲和父母照顾做好准备。在小鼠中，成年V-SVZ 的增殖在妊娠第 7 天 (Gestation day，Gd) 时增加，并在产后第7天 (Postpartum day，Ppd) 再次增加，干扰成人V-SVZ神经发生有时会导致母体行为缺陷。通过对小鼠的NSCs增殖进行量化（GFAP+ Ki67+），发现不同妊娠天数以及产后不同天数V-SVZ 中NSC的增殖状态以及亚群并不一致。并且，与妊娠相关的领域还表现出独特的时间动态性。说明在小鼠妊娠期间，母体内的多个区域不同的NSCs，包括通常处于静止状态区域的NSCs，在不同的妊娠时期被激活。图3 NSCs增殖动态性研究人员发现NSC池的同步激活会产生瞬时的短寿命 OB 中间神经元。由于断奶后幼崽越来越多地吃固体食物，所以母亲较少参与幼崽护理。相应的发现在围产期母亲神经发生增强的所有层中，GCL中与妊娠相关的中间神经元会因断奶而被完全剔除，仅有在 MCL和AOB中，一些神经元仍然存在，说明这些神经元只是短暂存在的。图4 怀孕相关的OB 中间神经元是短暂存在的通过利用空间转录组技术，将围产期小鼠与未怀孕小鼠的整个 MOB 和 AOB 转录组的比较，确定了与妊娠相关的中间神经元的分子标记，包括NPY、Cbln1、Calb2、Zic1和TH。结果表明某些亚群是暂时需要的，用于识别幼崽，然后随着幼崽的成熟而消失。研究还发现而未怀孕鼠不会辨别外来幼崽的气味，但围产期和断奶期的小鼠却能辨别。对自己的幼崽与外来幼崽的比较，处于围产期的母亲更喜欢自己的幼崽。MCL中间神经元对于幼崽的识别至关重要，如果MCL中间神经元被移除后就不能识别自己的幼崽。总而言之，该研究发现在小鼠怀孕期间，母鼠体内的多个神经干细胞池被激活，并产生特定的嗅球中间神经元，这些神经元在小鼠出生前后发挥作用，调节母性护理的各个方面，包括识别自己的幼崽，然后随着幼崽的成熟而消失。参考资料：1、https://mp.weixin.qq.com/s/kcC8HVxumPZvjSVCu8IiwQ2、Zayna Chaker et al. ,Pregnancy-responsive pools of adult neural stem cells for transient neurogenesis in mothers.Science382,958-963(2023).DOI:10.1126/science.abo5199撰文 | Anna编辑 | 蓁蓁精彩推荐：1、吃对东西多活十年！Nature子刊：英国多个学术机构研究共同证实饮食结构与寿命密切相关！2、别再胖下去了！近60万数据荟萃分析显示：肥胖真的导致癌症，至少13种！3、久坐伤身不用怕！《英国运动医学杂志》发现每天只需这样运动22分钟即可抵消久坐带来的死亡风险4、喝酸奶防抑郁！新研究揭示益生菌调节情绪新机制，有助于改善心理健康！5、Cell重磅：成功构建全球首个多腔室心脏类器官平台研究心脏发育和疾病本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！

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