Neurobiology of Somatostatin Receptors: Functional Characterization in Central Nervous System

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物质，GABA为抑制性神经递质。NMDA受体、主要谷氨酸离子亲和性受体和生长抑素受体广泛表达于中枢神经系统，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SSTRs抑制NMDARs介导的中枢神经毒性效应，提示神经元和/或星形胶质细胞释放的SST在神经毒性中可能在神经元存活中发挥重要作用。在将SSTR亚型应用于病理条件之前，确定它们的准确分布和生物学功能是至关重要的。为了描述SSTRs的形态、生化或生物物理性质，并推导出与脑内NMDAR亚型的任何直接药理关系，我们将使用体内(脑片)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。我们将解决以下问题：

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: