Helm KA, Han JS, Gallagher M (2001) Selective cholinergic deafferentation affects GR mRNA expression in the rat brain. Neuroscience 2001 Abstracts 175.10. Society for Neuroscience, San Diego, CA.
Summary: Two common features of the aging process include progressive dysfunction of both the basal forebrain cholinergic (BFC) system and suprahypothalamic feedback on the hypothalamic-pituitary-adrenal (HPA) axis. Prior research has shown that an age-related reduction in glucocorticoid receptor (GR) mRNA expression occurs in cortical target sites of the BFC system, including the hippocampus, prefrontal cortex, and anterior olfactory cortex, which are highly correlated with both spatial learning impairments and a blunted negative feedback of the stress response among aged rats. Selective deafferentation of the BFC system in young rats produces a similar reduction in both GR mRNA expression in the hippocampus and the efficiency of the stress response, as measured by a protracted increase in the levels of plasma corticosterone following acute stress. The current study investigated the possibility that loss of cholinergic input from cells in the basal forebrain alters GR mRNA expression in other BFC target structures, including the medial prefrontal cortex and the anterior olfactory cortex. Lesions of the BFC system were made by microinjections of the immunotoxin IgG-192-saporin into the medial septum/vertical limb of the diagonal band, and the substantia innominata/nucleus basalis. Basal levels of plasma corticosterone measured in the morning and evening 3 weeks later did not reveal any differences between lesioned and non-lesioned rats. The abundance of GR mRNA in sections processed for quantitative in situ hybridization will include a full analysis of cortical as well as subcortical sites to reveal the extent of effects of cholinergic lesions on GR mRNA expression throughout the brain. Supported by NIA PO1-AG09973.
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