Abstract:
Although more than 30 different types of neuropeptides have been identified in various cell types and circuits of the cerebellum, their unique functions in the cerebellum remain poorly understood. Given the nature of their diffuse distribution, peptidergic systems are generally assumed to exert a modulatory effect on the cerebellum via adaptively tuning neuronal excitability, synaptic transmission, and synaptic plasticity within cerebellar circuits. Moreover, cerebellar neuropeptides have also been revealed to be involved in the neurogenetic and developmental regulation of the developing cerebellum, including survival, migration, differentiation, and maturation of the Purkinje cells and granule cells in the cerebellar cortex. On the other hand, cerebellar neuropeptides hold a critical position in the pathophysiology and pathogenesis of many cerebellar-related motor and psychiatric disorders, such as cerebellar ataxias and autism. Over the past two decades, a growing body of evidence has indicated neuropeptides as potential therapeutic targets to ameliorate these diseases effectively. Therefore, this review focuses on eight cerebellar neuropeptides that have attracted more attention in recent years and have significant potential for clinical application associated with neurodegenerative and/or neuropsychiatric disorders, including brain-derived neurotrophic factor, corticotropin-releasing factor, angiotensin II, neuropeptide Y, orexin, thyrotropin-releasing hormone, oxytocin, and secretin, which may provide novel insights and a framework for our understanding of cerebellar-related disorders and have implications for novel treatments targeting neuropeptide systems.
摘要:
尽管在小脑的各种细胞类型和回路中已鉴定出30多种不同类型的神经肽,它们在小脑中的独特功能仍然知之甚少。鉴于它们扩散分布的性质,通常认为肽能系统通过自适应调节神经元兴奋性对小脑产生调节作用,突触传递,和小脑回路内的突触可塑性。此外,小脑神经肽也被发现参与发育小脑的神经遗传和发育调节,包括生存,迁移,分化,以及小脑皮质中的浦肯野细胞和颗粒细胞的成熟。另一方面,小脑神经肽在许多小脑相关的运动和精神疾病的病理生理学和发病机制中占有重要地位,比如小脑共济失调和自闭症。在过去的二十年里,越来越多的证据表明神经肽是有效改善这些疾病的潜在治疗靶点。因此,这篇综述集中于八种小脑神经肽,这些小脑神经肽近年来引起了更多的关注,并且具有与神经退行性和/或神经精神疾病相关的临床应用的巨大潜力,包括脑源性神经营养因子,促肾上腺皮质激素释放因子,血管紧张素II,神经肽Y,orexin,促甲状腺激素释放激素,催产素,和促胰液素,这可能为我们对小脑相关疾病的理解提供了新的见解和框架,并对靶向神经肽系统的新治疗具有意义。