Astrocyte-Neuron communication: Unravelling the role of astrocytes in the modulation of neuronal circuits

星形胶质细胞是一种神经胶质细胞，是大脑中数量最多的细胞类型。它们的数量是神经元的十倍，占成年人大脑重量的近90%。它们最初被认为在脑代谢和脑血流调节中仅起支持作用。现在已知它们还通过释放含有特定物质的囊泡来调节神经元及其突触，并且在一些神经病性（例如疼痛和癫痫）和神经变性状态（例如阿尔茨海默病、帕金森病和多发性硬化症）中具有关键作用。这些疾病中的许多与被称为“反应性”的病理性星形胶质细胞过程有关。这一过程仍然是个谜，导致所谓的反应性神经胶质增生，其特征是基因表达的变化，细胞扩大和细胞形状的变化，以及在某些情况下，细胞分裂。大多数关于星形胶质细胞反应性的研究都集中在星形胶质细胞代谢活动的损伤上。相对而言，关于反应性神经胶质增生对所谓的“更新的”星形胶质细胞作用的影响知之甚少，例如它们利用胶质递质（GT：谷氨酸和ATP）和神经营养因子（NTFs：胶质和脑源性神经营养因子）的胞吐作用与彼此和附近神经元相互作用的能力。本计画将进一步探讨星形胶质细胞与神经元通讯的正常机制，并检视星形胶质细胞反应性对这些机制的影响。目的是确定可能的治疗靶点，以改善神经变性的有害影响。

Astrocytes, a type of glial cell, are the most numerous cell type in the brain. They outnumber their neuronal counterparts by ten times and make up almost 90% of adult brain weight. They were originally thought to have only a supportive role in brain metabolism and the regulation of brain blood flow. It is now known that they also modulate neurons and their synapses through release of vesicles containing specific substances and have key roles in some neuropathic (e.g. pain and epilepsy) and neurodegenerative states (e.g. Alzheimer's disease, Parkinson's disease, and multiple sclerosis). Many of these diseases are associated with a pathological astrocyte process known as 'reactivity'. This process remains enigmatic, resulting in so-called reactive gliosis, a reaction characterized by changes in gene expression, cell enlargement and changes in cell shape, and, in some cases, cell division. Most of the research on astrocyte reactivity has focused on the impairment of astrocyte metabolic activities. Comparatively little is known about the effect of reactive gliosis on so called 'newer' astrocyte roles such as their ability to interact with each other and nearby neurons using exocytosis of gliotransmitters (GTs: glutamate and ATP) and neurotrophic factors (NTFs: glial and brain derived neurotrophic factors). This project will both further investigate the normal mechanisms of astrocyte-neuron communication, and examine the effects of astrocyte reactivity on these mechanisms. The aim is to identify possible therapeutic targets to ameliorate the detrimental affects of neurodegeneration.