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(114) ALTERED EXPRESSION OF NEURONAL NITRIC OXIDE SYNTHASE (nNOS) IN FEMALE RAT BRAIN DURING AGING. Brann, Darrell1, Khan, Mohammad 1, 1 Medical College of Georgia, Augusta, GA ABSTRACT- Nitric oxide (NO) has been implicated in many functions in the brain, including control of learning and memory, regulation of synaptic function and control of reproduction. Regional changes in the expression as well activity of the neuronal NO synthesizing enzyme, neuronal nitric oxide synthase (nNOS) has been reported in the aging rat brain. However, there are controversies as some reports showed a decrease, while others showed an increase in the activity and expression of nNOS in old versus young rat brain. Our laboratory undertook analysis of nNOS levels in different brain regions in young versus middle aged female rats. Young (3 month) and middle-aged (9-11 month old) Sprague Dawley rats (N=5) were ovariectomized and one week later treated with vehicle or estrogen (E2) for two days. On the third day at 1200h, the animals were sacrificed by intracardial perfusion with 0.1M PBS, pH 7.4 followed by fixation with cold 4% paraformaldehyde in 0.01M PBS. Brains were post-fixed overnight in the same fixative and cryoprotected in 30% sucrose for 24-36h at 4C. Immunohistochemistry was performed on 20uM coronal section using rabbit polyclonal anti-nNOS antibodies. While there was no change in the nNOS expression in cerebral cortex, a significant increase (P=0.05-0.004) was observed in nNOS expression in the striatum and hypothalamic regions (POA and DBB) in middle aged rat brain. E2 treatment did not affect nNOS immunoreactivity in young rats whereas in middle aged rats it was found to reduce nNOS immunoreactivity in hypothalamic regions but not in the striatum or cerebral cortex. These observations suggest that nNOS expression increases during the transition from young to middle age in ovx rats and that E2 regulates the expression of nNOS in the hypothalamus. The mechanism(s) responsible for the elevation of nNOS levels in the brain at middle-age are unclear and require further investigation. KEY WORDS: Estrogen, Aging, Hypothalamus, Nitric Oxide |
