This study was conducted to define the molecular mechanism of fasting-induced down-regulation of neuronal nitric oxide synthase (nNOS) expression in the hypothalamic paraventricular nucleus (PVN). Rats were adrenalectomized (ADX), and then either underwent food deprivation or received varying doses of dexamethasone for 48 h. The brain tissues were processed for NADPH-diaphorase (NADPH-d) staining, a histochemical marker of nNOS enzyme activity. Both the ADX and the sham operated rats showed a significant weight loss after 48 h of food deprivation. Food deprivation decreased the number of NADPH-d containing cells in the PVN of sham rats, however, not in the ADX rats. Dexamethasone dose- dependently decreased NADPH-d cells in the PVN of ADX rats. The effect of ADX or dexamethasone was limited to the parvocellular subdivision of PVN. These results suggest that the adrenal glucocorticoids may down-regulate nNOS expression in the PVN during food deprivation.
*Adrenalectomy ; Animals ; Biological Markers ; Dexamethasone/blood/pharmacology ; Down-Regulation/physiology ; Fasting/*physiology ; Food Deprivation/physiology ; Glucocorticoids/blood/pharmacology ; Male ; NADPH Dehydrogenase/*metabolism ; Nitric-Oxide Synthase/*metabolism ; Paraventricular Hypothalamic Nucleus/*enzymology ; Rats ; Rats, Sprague-Dawley ; Support, Non-U.S. Gov't

In this study, we examined if glucocorticoids are required for the fasting-induced decrease of neuronal nitric oxide synthase (nNOS) in the magnocellular division of the paraventricular nucleus (PVN). Rats were adrenalectomized, subjected to 48 h of food deprivation with/without dexamethasone (5 mg/ kg, 4 subcutaneous injections with 12 h intervals), and the brain slices were processed for NADPH-diaphorase (NADPH- d) staining, a histochemical marker for nNOS in neuronal cells. In food deprived adrenalectomized rats, but not in free fed intact rats, dexamethasone significantly decreased NADPH-d staining in the magnocellular PVN. We previously reported that food deprivation decreases nNOS in the magnocellular PVN of intact rats. Thus, the present results together with our previous report suggest that although glucocorticoids are required for fasting-induced nNOS down-regulation in the magnocellular PVN, glucocorticoids may not be directly involved and some other molecular signals produced by food deprivation may play a pivotal role over glucocorticoid in the regulatory pathway for nNOS expression in this brain region.
Adrenalectomy ; Animals ; Dexamethasone/pharmacology ; Down-Regulation ; Fasting/*metabolism ; Male ; NADPH Dehydrogenase/*analysis ; Nitric-Oxide Synthase/genetics ; Paraventricular Hypothalamic Nucleus/*enzymology ; Peptides/physiology ; Rats ; Rats, Sprague-Dawley ; Research Support, Non-U.S. Gov't ; Weight Gain

BACKGROUNDWe investigated the role in electrical stimulations of paraventricular nucleus (PVN) on gastric mucosal cells and the activity of mitogen-activated protein kinases (MAPKs) family members induced by gastric ischemia-reperfusion (GI-R). And we elucidated the molecular mechanisms of the protection of PVN from GI-R injuries.

METHODSSprague-Dawley rats were divided randomly into 4 groups: Group I, the sham-operated GI-R control group; Group II, the sham-operated electrical stimulations to PVN + sham-operated GI-R control group; Group III, the GI-R group; and Group IV, the electrical stimulations to PVN + GI-R group. In all of the experiments, the PVN was stimulated prior to the induction of GI-R. The GI-R model was established by clamping the celiac artery for 30 minutes to induce ischemia and then was released to allow reperfusion for 30 minutes, 1 hour, 3 hours and 6 hours, respectively. The gastric mucosal cellular apoptosis, proliferation, and the expression and activity of MAPKs protein were observed by immunohistochemistry and Western blotting, respectively.

RESULTSCompared with the GI-R group, the application of electrical stimulations in the PVN significantly depressed gastric mucosal cellular apoptosis and enhanced gastric mucosal cellular proliferation following the 30-minute, 1-hour and 3-hour intervals of reperfusion; it also promoted the activation of p-ERK during the early phase of reperfusion but inhibited the activation of p-JNK1/2 and p-p38 following the 30-minute, 1-hour and 3-hour intervals of reperfusion.

CONCLUSIONSThe protection of PVN against GI-R injuries may attribute to the inhibition of apoptosis and the promotion of the proliferation of gastric mucosal cells during GI-R. This protective effect is mediated by activating the ERK pathway and depressing the JNK, p38 MAPK pathways of the gastric mucosal cells.

Animals ; Apoptosis ; Cell Proliferation ; Electric Stimulation ; Extracellular Signal-Regulated MAP Kinases ; physiology ; Gastric Mucosa ; blood supply ; enzymology ; pathology ; JNK Mitogen-Activated Protein Kinases ; physiology ; MAP Kinase Signaling System ; physiology ; Male ; Paraventricular Hypothalamic Nucleus ; physiology ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control ; p38 Mitogen-Activated Protein Kinases ; physiology