Cholinergic neurons in the basal forebrain of aged female mice.
Aging is associated with at least down-regulation of several cellular functions and diminished responsiveness to internal and external signals, and possibly with direct cell death. Consequently, pharmacological manipulations may be less effective in aged than in young organisms. In the present study, we investigated whether the basal forebrain cholinergic neurons and the estrogen receptor alpha (ERalpha) which they contain respond to changes in estrogen availability in aged female mice. The mice were sham-operated, ovariectomized, or ovariectomized and treated with 17beta-estradiol at the age of 18 months. Three months later, the mice were perfused and brain sections were double immunostained for choline acetyltransferase (ChAT) and ERalpha. Cell counting with a stereological method revealed that changes in the estrogen level have no effect on the total number of ChAT-immunoreactive (ir) neurons in the basal forebrain. However, the percentage of ChAT-ir neurons containing ERalpha-ir was higher in the ovariectomized mice than in the sham-operated or estrogen-treated mice. This was specific for the medial septum and vertical diagonal band of Broca. The findings indicate that even at old age the ERalphas in cholinergic cells are able to respond to changes in estrogen levels, though in a region-specific manner. This is naturally important for studies aiming to develop therapies for the elderly.
Kalesnykas
Giedrius
G
Department of Neuroscience and Neurology, University of Kuopio, P.O. Box 1627, Kuopio FIN-70211, Finland.
Puoliväli
Jukka
J
Sirviö
Jouni
J
Miettinen
Riitta
R
D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002452:Cell Count / Q000379:methods; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D009929:Organ Size / Q000502:physiology; D010052:Ovariectomy / Q000379:methods; D016548:Prosencephalon / Q000166:cytology* / Q000378:metabolism; D014599:Uterus / Q000187:drug effects
D047628:Estrogen Receptor alpha; D004958:Estradiol; D002795:Choline O-Acetyltransferase