69 Amino acid systems Glutamic acid decarboxylase, responsible for the synthesis of γ-vinyl γ-aminobutyric acid (GABA), declines with age in cortex, hippocampus, and striatum, while there is limited evidence for decreases in markers of the glutamatergic system (transporter and NMDA receptor).46,70 It is, however, difficult to assess the

status of the presynaptic glutamatergic system since the neurotransmitter is a ubiquitous component, of all cells.71 While no changes have been reported in [3H]MK801 binding (to the ion channel) from middle age to old age, age-related changes in the ability of glutamate Inhibitors,research,lifescience,medical and glycine binding sites Inhibitors,research,lifescience,medical to influence binding within the channel have been observed.72,73 For example, the ability of glutamate and glycine to enhance [3H]MK801 binding in the frontal cortex is reduced

from a 44% increase in young adults to a 35% increase in 80- to 100-year-old humans.74 Furthermore, spermine stimulation of [3H]MK801 binding via the polyamine site disappears by 80 years of age and zinc inhibition also declines with increased age.74 Reduction Inhibitors,research,lifescience,medical in binding to one or more sites on the NMDA receptor complex with age may reflect, losses of the entire receptor complex, a selective loss of certain subunits, or both. There is some evidence from studies in mice that changes in receptor subunit composition occur with age and may form the basis for changes

in the affinity of certain Inhibitors,research,lifescience,medical binding sites.75 Influence of gender on brain aging The profound impact of sex together steroids on brain structure and function is evidenced by sexual dimorphisms in brain organization and development,76 which have been associated with gender-based differences in behavior and learning.77 Recent Inhibitors,research,lifescience,medical evidence of male-female differences in brain aging supports an ongoing dynamic relationship between sex steroids and neural structure and function. This includes work by Honeycutt et al,78 which demonstrates differential aging patterns for the morphology of mesial temporal structures, particularly the amygdala, in men and women. In vivo evidence of male-female differences in neuroreceptor distribution has been shown for 5-HT2A receptors, and a specific age-gender interaction on 5-HT1A receptors has recently been reported.69 Gender preferences for psychiatric disorders, particularly depressive illness, also support, a biological Drug_discovery underpinning for functional brain differences in men and women. Women clearly exhibit higher rates of depression in early and middle adulthood, with enhanced risk associated with surgical menopause and antiestrogen treatment for Paclitaxel polymer stabilizer breast, cancer.79,80 However, there is evidence for a narrowing of the gender gap in mood disorders in older middle adulthood, for which a neuroendocrine basis is speculated.