Age-related decrease of plasma testosterone in SAMP8 mice: replacement improves age-related impairment of learning and memory.
Corticosterone increases with aging but pregnenolone, dehydroepiandrosterone, and testosterone decrease. The marked decrease in hormones that occurs with aging may contribute to the age-related deficit in learning and memory. Administration of these hormones after training was found to improve long-term memory processing in normal young mice. SAMP8 (P8) mice show an age-related loss of learning and memory for a variety of tasks whereas age-matched control mice of the closely related SAMR1 (R1) strain do not. In this study, we found an age-related decrease in serum testosterone levels of 71% between P8 mice 4 and 12 months of age, but only a 26% decrease between R1 mice of the same ages. The difference between the P8 mice was significant (p < 0.01) and the difference between the R1 mice was not. The decrease in testosterone in 12-month-old P8 mice was not accompanied by gross morphological change in the testes. A SC testosterone implant, sufficient to increase plasma testosterone levels to 414 +/- 25 ng/dl, alleviated impaired learning and memory of a foot shock avoidance task in P8 mice. Castration of 4-month-old P8 mice did not produce a deterioration in learning and memory, indicating that low levels of testosterone per se are not responsible for the impairment seen in 12-month-old P8 mice. This suggests that impaired cognitive functioning of the older P8 mice was due to an interaction of aging and reduced testosterone levels.
Flood
J F
JF
Geriatric Research Education and Clinical Center (GRECC), VA Medical Center, St. Louis, MO 63109, USA.
Farr
S A
SA
Kaiser
F E
FE
La Regina
M
M
Morley
J E
JE
D000375:Aging / Q000097:blood* / Q000523:psychology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D004343:Drug Implants; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D009919:Orchiectomy; D013045:Species Specificity; D013737:Testis / Q000033:anatomy & histology / Q000187:drug effects; D013739:Testosterone / Q000097:blood* / Q000494:pharmacology*
D004343:Drug Implants; D013739:Testosterone