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Treatment with Dehydroepiandrosterone Increases Peripheral Benzodiazepine Receptors of Mitochondria from Cerebral Cortex in d ‐Galactose‐Induced Aged Rats
Author(s) -
Chen Chunfu,
Lang Senyang,
Zuo Pingping,
Yang Nan,
Wang Xiangqing
Publication year - 2008
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2008.00288.x
Subject(s) - medicine , endocrinology , benzodiazepine , dehydroepiandrosterone , receptor , cerebral cortex , gabaa receptor , water maze , peripheral , morris water navigation task , mitochondrion , chemistry , hippocampus , hormone , biochemistry , androgen
The aim of this study was to determine whether dehydroepiandrosterone (DHEA) could regulate the expression of peripheral benzodiazepine receptors of mitochondria in cerebral cortex. The rats were divided into five groups. Those, in the vehicle‐physiological or senescent group, received physiological or d ‐galactose (subcutaneously) once a day. Rats, in the vehicle‐dimethyl sulfoxide‐ or DHEA‐treated senescent group, received 2% of dimethyl sulfoxide or DHEA (intraperitoneally) every other day besides d ‐galactose (subcutaneously) once a day. Rats in the DHEA‐treated normal group received physiological once a day and DHEA every other day. After 8‐week, spatial learning was assessed for 5 days by water maze methods. Following behavioural testing, the cerebral cortex mitochondria were purified for PK11195 binding analysis. When compared to the respective vehicle, d ‐galactose alone induced a significant impairment in water maze performance accompanied by a reduction (30.7%) in peripheral benzodiazepine receptor density of mitochondria, and DHEA displayed a significant enhancement in learning memory accompanied by the elevation (18.3%) of peripheral benzodiazepine receptor density but not affinity in senescent rats. DHEA showed insignificant effects on both learning/memory ability and peripheral benzodiazepine receptors in normal rats when compared to physiological saline. These results suggest that chronic treatment with DHEA enhance cognitive function and increase peripheral benzodiazepine receptor density in cerebral cortex mitochondria in middle‐aged senescent rats.