Effect of corticosteroid treatment in vitro on adrenalectomy-induced impairment of synaptic transmission in the rat dentate gyrus.
Removal of the rat adrenals results after 3 days in the appearance of apoptotic cells in the dentate gyrus. Apoptosis is accompanied by an impaired synaptic transmission in the dentate gyrus. Substitution in vivo with a low dose of corticosterone was found to prevent both the appearance of apoptotic cells and the functional impairment. In the present study we determined whether the functional normalisation after corticosterone treatment critically depends on prevention of apoptosis. To address this question, brain slices from rats showing apoptosis after adrenalectomy were treated in vitro with the mineralocorticoid aldosterone (3 nM) or with 30 nM corticosterone, which is assumed to activate both mineralo- and glucocorticoid receptors. Steroids were briefly applied either during recording (acute effects) or several hours before recording (long-term effects). While the slope of the fEPSP recorded in the outer molecular layer of the dentate gyrus in response to perforant path stimulation was not affected up to 1 h after acute administration of the steroids, fEPSP slopes recorded 2.5-3 h after corticosterone or aldosterone treatment were significantly increased, to the level of the sham-operated controls. The results indicate that delayed corticosteroid effects through in vitro activation of mineralocorticoid receptors (MRs) are sufficient to normalise synaptic transmission in the dentate gyrus of ADX rats, even in the presence of apoptotic cells. We tentatively conclude that the impaired synaptic transmission seen after ADX is probably not primarily caused by the appearance of apoptotic cells.
Stienstra
C M
CM
Institute for Neurobiology, University of Amsterdam, the Netherlands.
Joëls
M
M
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000315:Adrenalectomy; D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials; D007700:Kinetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D015430:Weight Gain
D000305:Adrenal Cortex Hormones; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D003345:Corticosterone