Neurobiology of Somatostatin Receptors: Functional Characterization in Central Nervous System

生长抑素受体的神经生物学：中枢神经系统的功能表征

• 批准号: RGPIN-2017-05695
• 负责人: Kumar, Ujendra
• 金额: $ 1.89万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629571
• 关键词: Neurobiology; Somatostatin; Receptors; Functional; Characterization

Central nervous system (CNS) is composed of neurons and astrocytes, which use glutamate as major excitatory and GABA as an inhibitory neurotransmitter. NMDA receptors, major glutamate ionotropic receptors and somatostatin receptors (members of GPCR family) are widely expressed in CNS and linked to many fundamental functions of the brain at the molecular and cellular levels. Several studies have shown an inhibitory role of Somatostatin (SST) via SSTRs on NMDARs mediated neurotoxic effects on CNS suggesting that SST released from neurons and/or astrocytes might play a crucial role in neuronal survival in neurotoxicity. Prior to implementing SSTR subtypes to pathological conditions, it is essential to determine their precise distribution and biological functions. To delineate the morphological, biochemical or biophysical properties of SSTRs and to derive any direct pharmacological relation with NMDAR subtypes in the brain, we will use in-vivo (brain slices) and in-vitro (pure and mixed neuronal and astrocytes culture) models to induce NMDA toxicity. We will address following questions:

中枢神经系统（CNS）由神经元和星形胶质细胞组成，以谷氨酸为主要兴奋性神经递质，氨基丁酸为抑制性神经递质。NMDA受体、主要的谷氨酸嗜离子受体和生长抑素受体（GPCR家族成员）在中枢神经系统中广泛表达，并在分子和细胞水平上与大脑的许多基本功能有关。一些研究表明，生长抑素（SST）通过sstr对NMDARs介导的中枢神经系统神经毒性作用具有抑制作用，这表明神经元和/或星形胶质细胞释放的SST可能在神经毒性中神经元存活中起关键作用。在将SSTR亚型应用于病理条件之前，确定其精确分布和生物学功能至关重要。为了描述SSTRs的形态学、生化或生物物理特性，并得出其与脑内NMDAR亚型的直接药理学关系，我们将使用体内（脑切片）和体外（纯和混合神经元和星形胶质细胞培养）模型来诱导NMDA毒性。我们将讨论以下问题：