Avtor/Urednik		Wang, S. S.; Kamphuis, W; Huitinga, I; Zhou, J-N; Swaab, Dick Frans
Naslov		Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR
Tip		članek
Vol. in št.		Letnik 13, št. 8
Leto izdaje		2008
Obseg		str. str.786-799
ISSN		1359-4184 - Molecular psychiatry
Jezik		eng
Abstrakt		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-[beta] and tumor necrosis factor-[alpha], (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-a, 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.
Proste vsebinske oznake		steroid receptors hypothalamo-pituitary-adrenal axis depression steroidni receptorji hipotalamus-hipofizno-nadledvična os depresija