Nerve growth factor restores mRNA levels and the expression of neuropeptides in the suprachiasmatic nucleus of rats submitted to chronic ethanol treatment and withdrawal

Chronic ethanol treatment and withdrawal from alcohol decrease the synthesi s and expression of neuropeptides in the hypothalamic suprachiasmatic nucle us. Given the existing evidence that neurotrophins modulate the synthesis a nd expression of neurotransmitters/neuromodulators in the mature brain, we have hypothesized that such alterations might result from the reduced biolo gical activity or brain content of neurotrophic factors. To test this possi bility, nerve growth factor (NGF) was delivered intraventricularly, over a 4-week period, to rats submitted to ethanol treatment for 6 months and to w ithdrawn rats. Vasopressin (AVP) and vasoactive intestinal polypeptide (VIP ), and the respective mRNAs were detected by immunocytochemistry and in sit u hybridization histochemistry, and their levels estimated using stereologi cal methods and densitometry. In ethanol-treated and withdrawn rats, NGF pr oduced increases in the number of AVP- and VIP-immunostained neurons to val ues identical to those of controls. Corresponding variations were detected in AVP and VIP mRNA levels, which indicates that NGF restored the expressio n of AVP and VIP by enhancing neuropeptide synthesis. These findings show t hat NGF can correct the changes induced by chronic ethanol treatment and wi thdrawal in the gene expression and protein content of the neuropeptides sy nthesized by suprachiasmatic neurons. They also reveal that NGF plays an im portant role in the maintenance of the neurochemical phenotype of the supra chiasmatic nucleus in the adult rat. Because suprachiasmatic neurons do not express trkA, NGF might have exerted its effects either through direct sig nalling of suprachiasmatic neurons via p75(NTR) activation or, indirectly, by enhancing the activity of the cholinergic and/or glutamatergic afferents to the suprachiasmatic nucleus, or both.