Dorsomedial Nucleus Hypothalamus Research Articles

Effects of Estradiol on Glycemic and CNS Neuronal Activational Responses to Recurrent Insulin-Induced Hypoglycemia in the Ovariectomized Female Rat

Recurrent insulin-induced hypoglycemia (RIIH) results in glucose counterregulatory dysfunction in men and male rodents. Intensified hypoglycemia in the latter coincides with diminished neuronal Fos expression in central metabolic regulatory structures, evidence that supports habituation of CNS-mediated compensatory motor outflow during re-exposure to this metabolic stress. In light of the evidence for counterregulatory resistance to precedent hypoglycemia in women, we utilized estradiol-treated ovariectomized (OVX) female rats to examine the hypothesis that this hormone regulates neural adaptability to recurring hypoglycemia. Groups of OVX rats were implanted with subcutaneous silastic capsules containing estradiol benzoate (E) or oil alone, and injected subcutaneously with one or four doses of the intermediate-acting insulin, Humulin NPH, one dose daily, or with diluent alone. Blood glucose levels were not altered by RIIH in E-implanted OVX animals, but were significantly decreased after four versus one insulin injection in the OVX+oil group. Mean numbers of Fos-immunoreactive (ir) neurons in the paraventricular nucleus hypothalamus (PVH), dorsomedial nucleus hypothalamus (DMH), and lateral hypothalamic area (LHA) were higher in both E- versus oil-implanted OVX rats injected with diluent only. Acute hypoglycemia significantly increased mean counts of Fos-ir-positive neurons in the PVH, DMH, and LHA, as well as the nucleus of the solitary tract (NTS) and area postrema (AP) in E- and oil-treated animals to an equivalent extent. OVX+E rats exhibited comparable numbers of Fos-positive neurons in the PVH, DMH, and LHA after one versus four insulin injections, whereas the numbers of labeled neurons in NTS and AP were increased or decreased, respectively, by RIIH. Oil-implanted OVX rats showed significantly diminished numbers of Fos-ir-positive neurons in each neural structure after repeated hypoglycemia. The present data demonstrate that estradiol sustains or enhances neuronal reactivity to recurring hypoglycemia in central metabolic structures, whereas hypoglycemic patterns of Fos expression in each site become habituated during RIIH in the absence of this steroid. The brain sites characterized here by estrogen-dependent maintenance of neuronal genomic reactivity to this substrate fuel imbalance may contain direct and/or indirect cellular targets for hormonal actions that prevent adaptation of CNS-controlled motor responses to this metabolic stress.

Neuronal expression of Fos protein in the rat brain after baroreceptor stimulation

The purpose of this study was to identify the CNS neurons that express Fos protein after repeated activation of the baroreceptor reflex. This was done in Wistar rats anesthetized with urethane and α-chloralose with careful physiological controls. The intact control rat showed few Fos-immunoreactive (ir) neurons, whereas the anesthetized control rat showed many Fos-ir neurons in the CNS from the medulla oblongata to the forebrain. After repeated stimulation of baroreceptors by pressor responses to phenylephrine (dose), we counted the amounts of Fos-ir neurons (response). The correlation coefficient of the dose-response relationship was high, and significant only in the medial part of the nucleus tractus solitarii (NTS) in the medulla and periaqueductal gray (PAG) in the midbrain, whereas it was comparatively high but insignificant in the commissure and lateral parts of the NTS, caudal and rostral ventrolateral medulla, periambiguus nucleus, dorsal and ventral medullary reticular nuclei, lateral parabrachial nucleus, paraventricular nucleus thalamus, and dorsomedial nucleus hypothalamus. No significant correlation was found in the humoral control nuclei in the preoptico-hypothalamic structure. Fos expression was never detected in the sensory neurons in the ganglia petrosum and nodosum, and in the sympathetic preganglionic neurons in the intermediolateral nucleus of the thoracic spinal cord. This study shows that Fos expression in the CNS neurons is induced not only by baroreceptor stimulation but also by anesthesia and/or sham-operation, and that Fos expression in the NTSm and PAG neurons faithfully responds to baroreceptor stimulation.