中國科學技術大學生命科學學院周江寧教授與荷蘭的科學家合作,，利用荷蘭人腦庫提供的人腦組織標本,，首次應用激光顯微切割技術研究了抑郁癥病人腦中負責應激反應和情緒調節(jié)的一個中樞（下丘腦）的改變。下丘腦只有成人的拇指指頭大小,，但非常復雜,，含有多種微小的，由不同功能神經細胞群組成的核團,。因此,，需要利用新型的激光分離技術將其中的一個特定核團既室旁核，分離出來進行特異性的研究（周江寧教授課題組的王姍姍同學完成了具體研究工作）,。
下丘腦室旁核中含有一群細胞,，既促腎上腺激素釋放因子（CRF）細胞，它們扮演著人體應激反應的中樞驅動的角色,，在抑郁癥病人腦中異?；钴S。該研究利用激光顯微分離室旁核區(qū)域并結合熒光定量分析技術,，對抑郁癥和正常人室旁核中16個參與調節(jié)CRF活性的相關基因表達進行了分析,。發(fā)現在抑郁癥下丘腦室旁核中，5個基因的上調或下調與抑郁癥發(fā)病相關,。這些基因表達的改變,，不僅能夠解釋為何在抑郁癥中CRF細胞活性增高，而且為尋找治療抑郁癥的藥物提供了新的靶點,。
生物谷推薦原始出處：
Molecular Psychiatry advance online publication 22 April 2008; doi: 10.1038/mp.2008.38
Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances
S-S Wang1,2, W Kamphuis1, I Huitinga1, J-N Zhou2 and D F Swaab1
1Netherlands Institute for Neuroscience, Amsterdam, The Netherlands
2Hefei National Laboratory for Physical Sciences at Microscale and Department of Neurobiology and Biophysics, Life Science School, University of Science and Technology of China, Hefei, Anhui, PR China
Abstract
Hyperactivity of corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus (PVN) of the hypothalamus is a prominent feature in depression and may be important in the etiology of this disease. The activity of the CRF neurons in the stress response is modulated by a number of factors that stimulate or inhibit CRF expression, including (1) corticosteroid receptors and their chaperones, heat shock proteins 70 and 90, (2) sex hormone receptors, (3) CRF receptors 1 (CRFR1) and 2, (4) cytokines interleukin 1- and tumor necrosis factor-, (5) neuropeptides and receptors, vasopressin (AVP), AVP receptor 1a (AVPR1A) and oxytocin and (6) transcription factor cAMP-response element-binding protein. We hypothesized that, in depression, the transcript levels of those genes that are involved in the activation of the hypothalamo–pituitary–adrenal (HPA) axis are upregulated, whereas the transcript levels of the genes involved in the inhibition of the HPA axis are downregulated. We performed laser microdissection and real-time PCR in the PVN and as a control in the supraoptic nucleus. Snap-frozen post-mortem hypothalami of seven depressed and seven matched controls were used. We found significantly increased CRF mRNA levels in the PVN of the depressed patients. This was accompanied by a significantly increased expression of four genes that are involved in the activation of CRF neurons, that is, CRFR1, estrogen receptor-, AVPR1A and mineralocorticoid receptor, while the expression of the androgen receptor mRNA involved in the inhibition of CRF neurons was decreased significantly. These findings raise the possibility that a disturbed balance in the production of receptors may contribute to the activation of the HPA axis in depression.
