Decreased interactions in protein kinase A-Glucocorticoid receptor signaling in the hippocampus after selective removal of the basal forebrain cholinergic input

• Published in: Hippocampus 2012-03, Vol.22 (3), p.455-465
• Main Authors: Lim, Chol Seung, Kim, Youn Jung, Hwang, Yoo Kyeong, Bañuelos, Christina, Bizon, Jennifer L., Han, Jung-Soo
• Format: Article
• Language: English
• Subjects: 192 IgG-saporin; aging; Alzheimer's disease; Animals; Cholinergic Neurons - metabolism; Corticosterone - blood; Cyclic AMP-Dependent Protein Kinases - metabolism; Hippocampus - metabolism; HPA axis; Hypothalamo-Hypophyseal System - metabolism; Male; Neural Pathways - metabolism; Pituitary-Adrenal System - metabolism; Prosencephalon - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Glucocorticoid - metabolism; Receptors, Mineralocorticoid - metabolism; Signal Transduction - physiology; stress
• ISSN: 1050-9631; 1098-1063
• DOI: 10.1002/hipo.20912

Removal of thecholinergic innervation to the hippocampus via selective immunolesions of septohippocampal cholinergic neurons induces dysfunction of the hypothalamic–pituitary–adrenocortical (HPA) axis and decreases glucocorticoid receptor (GR) mRNA. This study examined whether removal of the cholinergic innervation decreased GR protein levels and induced changes in the interaction between GR and the cytoplasmic catalytic subunit of protein kinase A (PKAc) in the hippocampus. In lesioned animals, GR protein levels were markedly decreased in the nucleus, but not in the cytosol of hippocampal neurons, whereas mineralocorticoid receptor (MR) levels remained unchanged in both the nucleus and cytosol. PKAc levels did not differ between lesioned and control groups, but PKAc activity was reduced in lesion tissue compared with the controls. The interaction between GR and PKAc was also decreased in the hippocampus without cholinergic input. These results indicate that degeneration of septohippocampal cholinergic neurons leads to reduced PKAc activity in the hippocampus which, in turn, alters GR signaling. The altered GR signaling induced by the degeneration of basal forebrain cholinergic neurons may contribute to dysfunction of the HPA axis in aged animals and patients with Alzheimer's disease (AD) and lead to neuropsychiatric symptoms that occur throughout the course of AD. © 2011 Wiley Periodicals, Inc.