Gender-specific alterations of cerebral metabolites with aging and cortisol treatment

Excess availability of the adrenocortical glucocorticoid hormone cortisol h as been correlated with structural brain changes and a decline of cognitive functions during aging. Pertinent studies need to consider gender as a pot ential confound because of sexual dimorphism in the regulation of hypothala mus-pituitary-adrenal axis activity. In vivo localized proton magnetic reso nance spectroscopy of male and female tree shrews revealed similar concentr ations of cerebral metabolites in young adult animals but gender-specific a lterations with aging as well as in response to cortisol, treatment. In com parison with adult tree shrews, aged males had reduced concentrations of N- acetylaspartate (-33%; P <0.01) and total creatine (-34%, P <0.01). These f indings are in line with the occurrence of neuronal loss. In contrast, aged females exhibited increased concentrations of choline-containing compounds (+27%, P <0.05) which-together with a tendency for increased creatine (+ 2 4%) and myo-inositol (+ 14%)-is indicative of glial proliferation. After ch ronic administration of cortisol (4 mg/day for 28 days), male but not femal e tree shrews showed a specific reduction of the choline-containing compoun ds (-29%,- P <0.05). The observed sex differences with age are likely to re sult from differences in the regulation of stress-related hormones which is further supported by the gender-specific responses to cortisol. (C) 2001 E lsevier Science Ltd. All rights reserved.