Humans and nonhuman primates are vulnerable to age- and menopause-related decline in working memory, a cognitive function reliant on the energy-demanding recurrent excitation of neurons within Brodmann’s Area 46 of the dorsolateral prefrontal cortex (dlPFC).

Hara and colleagues tested the hypothesis that the number and morphology of mitochondria in dlPFC presynaptic boutons are altered with aging and menopause in rhesus monkeys and that these correlate with measures of dlPFC-dependent working memory. They also examined the effects of estrogen administration to test whether a treatment known to improve working memory influences mitochondrial morphology.

Results showed that aged ovariectomized monkeys treated with vehicle displayed significant working memory impairment and a concomitant 44% increase in presynaptic donut-shaped mitochondria, both of which were reversed with cyclic estradiol treatment. The authors suggest that hormone replacement therapy may benefit cognitive aging, in part by promoting mitochondrial and synaptic health in the dlPFC.

Hara Y, Yuk F, Puri R, Janssen WG, Rapp PR, Morrison JH: Presynaptic mitochondrial morphology in monkey prefrontal cortex correlates with working memory and is improved with estrogen treatment.  Proc. Natl. Acad. Sci. USA 111(1):486-491 (2014).

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