Ciliary neurotrophic factor is expressed in the magnocellular neurosecretory system of the rat in vivo: evidence for injury- and activity-induced upregulation.

Although ciliary neurotrophic factor (CNTF) has been shown to promote the survival of magnocellular neurons when applied exogenously to explants of the paraventricular and supraoptic nuclei (SON) in vitro, little is known regarding its expression or regulation in the adult magnocellular neurosecretory system (MNS) following injury in vivo. Therefore, we utilized in situ hybridization and immunocytochemical analysis in conjunction with quantitative optical densitometric analysis to identify the cellular source of CNTF and examine the temporal pattern of its expression, following unilateral transection of the hypothalamo-neurohypophysial tract in the adult rat. In intact rats, CNTF immunoreactivity (CNTF-ir) was predominantly localized within identified astrocytes within the ventral glial limitans subjacent to the SON. Quantitative optical densitometric analysis of CNTF-ir levels in the axotomized SON demonstrated that the proportional area of CNTF-ir was significantly elevated between 3 and 30 days following injury. A significant but more limited increase was also observed in the non-injured contralateral SON. In situ hybridization confirmed the expression and upregulation of CNTF in the axotomized SON. These results demonstrate the expression of CNTF in the adult rodent MNS in vivo and provide evidence that levels of CNTF are upregulated in response to both direct injury, and heightened metabolic activity, within the lesioned and sprouting SON, respectively.

The influence of gender on parasympathetic vasodilatation in the submandibular gland of the rat.

Parasympathetic vasodilatation in the rat submandibular gland is mediated by nitric oxide-dependent and -independent mechanisms (prostacyclin and endothelium-derived hyperpolarizing factor (EDHF)). The purpose of this study was to determine the influence of gender on the relative contributions of each pathway to nerve-stimulated vasodilatation. Absolute increases in perfusion (laser Doppler flowmetry) were similar in male and female rats (in arbitrary perfusion units: 6159+/-4530 and 5601+/-3877 at 2 Hz; 15645+/-6830 and 14848+/-6118 at 5 Hz; and 22418+/-7660 and 18878+/-5864 at 10 Hz). However, expressed as a percentage increase above resting values, stimulated perfusion was higher in males than in females (P<0.05). In males both Nomega-nitro-L-arginine methyl ester (L-NAME) and indomethacin partly blocked parasympathetic vasodilatation at all frequencies tested (P<0.05). In female rats significant reductions in nerve-stimulated perfusion were observed only at 2 and 5 Hz, but the effects of L-NAME were greater than in males (-64 compared with -45% at 2 Hz and -45 compared with -33% at 5 Hz, P<0.05). Indomethacin by itself had no apparent effect in females. The combined effects of L-NAME and indomethacin were dependent on the order of administration and on gender. Following L-NAME, indomethacin had no further effect in males or females. L-NAME reduced indomethacin-resistant vasodilatation in males and females, but the added effect of indomethacin was more pronounced in males. Finally, atropine-resistant vasodilatation was partly blocked by L-NAME, and the remaining vasodilatation was abolished by spantide I (substance P receptor antagonist). We conclude that NO, products of cyclo-oxygenase activity and EDHF all play a role in parasympathetic vasodilatation, but that NO and EDHF are the major endothelium-derived vasodilators in the rat submandibular gland. In addition, when other pathways are blocked EDHF makes a greater contribution in females. Lastly, both vasoactive intestinal peptide and substance P contribute to the atropine-resistant vasodilatation.