NEUROSCIENCE

我们的长期研究目标是了解外部刺激后启动昼夜节律基因表达的分子机制。我们将使用松果体来研究信号通路，因为它已被广泛用于研究信号级联，因此为我们的研究提供了广泛的知识基础。我们的研究计划有两个目标：(1)了解去甲肾上腺素（NE）控制Period1表达的机制；(2)研究外部刺激对昼夜节律“时钟”基因表达的调节。首先，由于NE增加了细胞内环AMP （cAMP）和环GMP （cGMP）水平，我们将研究cAMP和cGMP信号通路诱导第1期mRNA水平的机制。由于第1周期被认为参与了昼夜节律的重置，我们将重点关注第1周期在特定目标I和I1中的表达调控。其次，我们将研究NE、cAMP、cGMP或cAMP和cGMP共刺激是否会诱导其他昼夜节律“时钟”mRNA水平。除了生物学上的重要性和兴趣，利用松果体作为模型，有望提供可能适用于预防神经退行性疾病（如阿尔茨海默氏症）的信息

Our long-term research objective is to understand the molecular mechanisms that initiate circadian gene expression following external stimulation. We will use the pineal gland to study signaling pathways because it has been extensively used to study signaling cascades and so provides an extensive knowledgebase for our studies. Our research proposal has two goals: (1) to understand the mechanisms by which norepinepherine (NE) controls Period1 expression and (2) to investigate the regulation of circadian "Clock" genes' expressions following external stimulation. First, since NE increases intra-cellular cyclic AMP (cAMP) and cyclic GMP (cGMP) levels, we will investigate the mechanisms by which cAMP and cGMP signaling pathways induce Period 1 mRNA levels. Since Period 1 is thought to be involved in the resetting of circadian rhythms, we will focus on the regulation of Period 1 expression in specific aims I and I1. Secondly, we will investigate whether or not other circadian "Clock" mRNA levels are induced by NE, cAMP, cGMP, or cAMP and cGMP co-stimulation. Besides its biological importance and interest, the use of pineal gland as a model, has promise for providing information that may be applicable to the prevention of neurodegenerative diseases, such as Alzheimer's disease, since it has been suggested that melatonin may play a role in neuroprotection. In addition, our studies have the pete" tial to address problems associated with jet lag, circadian-based sleep disorders, some neuropsychiatric illnesses, and shift work.