Anti-glucocorticoid gene therapy reverses the impairing effects of elevated corticosterone on spatial memory, hippocampal neuronal excitability, and synaptic plasticity.

ABSTRACT: Moderate release of the major stress hormones, glucocorticoids (GCs), improves hippocampal function and memory. In contrast, excessive or prolonged elevations produce impairments. Enzymatic degradation and reformation of GCs help to maintain optimal levels within target tissues, including the brain. We hypothesized that expressing a GC-degrading enzyme in hippocampal neurons would attenuate the negative impact of an excessive elevation in GC levels on synaptic physiology and spatial memory. We tested this by expressing 11-beta-hydroxysteroid dehydrogenase (type II) in dentate gyrus granule cells during a 3 d GC treatment followed by examination of synaptic responses in hippocampal slices or spatial performance in the Morris water maze. In adrenalectomized rats with basal GC replacement, ad

SUBMITTER: Dumas TC 

PROVIDER: S-EPMC3516494 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature