title: Estradiol regulation of hypothalamic astrocyte adenosine 5'-monophosphate-activated protein kinase activity: role of hindbrain catecholamine signaling.
abstract: Recent work challenges the conventional notion that metabolic monitoring in the brain is the exclusive function of neurons. This study investigated the hypothesis that hypothalamic astrocytes express the ultra-sensitive energy gauge adenosine 5'-monophosphate-activated protein kinase (AMPK), and that the ovarian hormone estradiol (E) controls activation of this sensor by insulin-induced hypoglycemia (IIH). E- or oil (O)-implanted ovariectomized (OVX) rats were pretreated by caudal fourth ventricular administration of the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) prior to sc insulin or vehicle injection. Individual astrocytes identified in situ by glial fibrillary acidic protein immunolabeling were laser-microdissected from the ventromedial (VMH), arcuate (ARH), and paraventricular (PVH) nuclei and the lateral hypothalamic area (LHA), and pooled within each site for Western blot analysis of AMPK and phosphoAMPK (pAMPK) protein expression. In the VMH, baseline astrocyte AMPK and pAMPK levels were respectively increased or decreased in OVX+E versus OVX+O; these profiles did not differ between E and O rats in other hypothalamic loci. In E animals, astrocyte AMPK protein was reduced [VMH] or augmented [PVH; LHA] in response to either 6-OHDA or IIH. IIH increased astrocyte pAMPK expression in each structure in vehicle-, but not 6-OHDA-pretreated E rats. Results provide novel evidence for hypothalamic astrocyte AMPK expression and hindbrain catecholamine-dependent activation of this cell-specific sensor by hypoglycemia in the presence of estrogen. Further research is needed to determine the role of astrocyte AMPK in reactivity of these glia to metabolic imbalance and contribution to restoration of neuro-metabolic stability.
authors.affiliation: Department of Basic Pharmaceutical Sciences, College of Pharmacy, The University of Louisiana at Monroe, Monroe, LA 71201, United States.
authors.forename: Pratistha
authors.initials: P
authors.lastname: Tamrakar
authors.affiliation: Department of Basic Pharmaceutical Sciences, College of Pharmacy, The University of Louisiana at Monroe, Monroe, LA 71201, United States. Electronic address: briski@ulm.edu.
authors.forename: Karen P
authors.initials: KP
authors.lastname: Briski
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000201:enzymology*; D002395:Catecholamines / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007003:Hypoglycemia / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology*; D007328:Insulin / Q000008:administration & dosage; D010052:Ovariectomy; D016627:Oxidopamine / Q000494:pharmacology; D010766:Phosphorylation; D017207:Rats, Sprague-Dawley; D012249:Rhombencephalon / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018663:Adrenergic Agents; D002395:Catecholamines; D005904:Glial Fibrillary Acidic Protein; D007004:Hypoglycemic Agents; D007328:Insulin; D004958:Estradiol; D016627:Oxidopamine; D055372:AMP-Activated Protein Kinases
keywords: 6-OHDA; Astrocyte; Insulin-induced hypoglycemia; Laser-catapult microdissection; PhosphoAMPK; Ventromedial hypothalamic nucleus