title: Dorsomedial hindbrain catecholamine regulation of hypothalamic astrocyte glycogen metabolic enzyme protein expression: Impact of estradiol.
abstract: The brain astrocyte glycogen reservoir is a vital energy reserve and, in the cerebral cortex, subject among other factors to noradrenergic control. The ovarian steroid estradiol potently stimulates nerve cell aerobic respiration, but its role in glial glycogen metabolism during energy homeostasis or mismatched substrate supply/demand is unclear. This study examined the premise that estradiol regulates hypothalamic astrocyte glycogen metabolic enzyme protein expression during normo- and hypoglycemia in vivo through dorsomedial hindbrain catecholamine (CA)-dependent mechanisms. Individual astrocytes identified in situ by glial fibrillary acidic protein immunolabeling were laser-microdissected from the ventromedial hypothalamic (VMH), arcuate hypothalamic (ARH), and paraventricular hypothalamic (PVH) nuclei and the lateral hypothalamic area (LHA) of estradiol (E)- or oil (O)-implanted ovariectomized (OVX) rats after insulin or vehicle injection, and pooled within each site. Stimulation [VMH, LHA] or suppression [PVH, ARH] of basal glycogen synthase (GS) protein expression by E was reversed in the former three sites by caudal fourth ventricular pretreatment with the CA neurotoxin 6-hydroxydopamine (6-OHDA). E diminished glycogen phosphorylase (GP) protein profiles by CA-dependent [VMH, PVH] or -independent mechanisms [LHA]. Insulin-induced hypoglycemia (IIH) increased GS expression in the PVH in OVX+E, but reduced this protein in the PVH, ARH, and LHA in OVX+O. Moreover, IIH augmented GP expression in the VMH, LHA, and ARH in OVX+E and in the ARH in OVX+O, responses that normalized by 6-OHDA. Results demonstrate site-specific effects of E on astrocyte glycogen metabolic enzyme expression in the female rat hypothalamus, and identify locations where dorsomedial hindbrain CA input is required for such action. Evidence that E correspondingly increases and reduces basal GS and GP in the VMH and LHA, but augments the latter protein during IIH suggests that E regulates glycogen content and turnover in these structures during glucose sufficiency and shortage.
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, The University of Louisiana at Monroe, Monroe, LA 71201, United States.
authors.forename: P
authors.initials: P
authors.lastname: Tamrakar
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, The University of Louisiana at Monroe, Monroe, LA 71201, United States.
authors.forename: P K
authors.initials: PK
authors.lastname: Shrestha
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, The University of Louisiana at Monroe, Monroe, LA 71201, United States. Electronic address: briski@ulm.edu.
authors.forename: K P
authors.initials: KP
authors.lastname: Briski
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000201:enzymology*; D002395:Catecholamines / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D024981:Glycogen Phosphorylase / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D007003:Hypoglycemia / Q000201:enzymology; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology*; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity; D010052:Ovariectomy; D016627:Oxidopamine / Q000633:toxicity; D017207:Rats, Sprague-Dawley; D012249:Rhombencephalon / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002395:Catecholamines; D004967:Estrogens; D005904:Glial Fibrillary Acidic Protein; D007004:Hypoglycemic Agents; D007328:Insulin; D009498:Neurotoxins; D004958:Estradiol; D016627:Oxidopamine; D006003:Glycogen; D024981:Glycogen Phosphorylase; D006006:Glycogen Synthase
keywords: estradiol; glycogen phosphorylase; glycogen synthase; insulin-induced hypoglycemia; laser-catapult microdissection; ventromedial hypothalamic nucleus