BIOHW 17 |
| Leptin regulates energy balance in part by modulating the activity of neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus. Leptin-deficient, (ob/ob) mice differ from wild-type mice in the number of excitatory and inhibitory postsynaptic densities and currents onto NPY and POMC neurons. When leptin was delivered to ob/ob mice, the synaptic density rapidly normalized, an effect detectable within 6 hours, several hours prior to leptin's effect on food intake. Synaptic currents were also shifted toward wild type values in leptin replaced ob/ob mice. These data suggest that leptin-mediated plasticity in the ob/ob hypothalamus may underlie some of the hormone's behavioral effects. In an effort to determine if the observed synaptic plasticity is leptin-specific, we analyzed the effects of an orexigenic hormone, ghrelin, and anorexigenic hormone, estradiol. Ghrelin re-arranged synapses in wild type animals to support suppressed POMC tone, while the estradiol triggered a robust increase in the number of excitatory, glutamate inputs of POMC neurons. The re-arrangement of synapses by estradiol was leptin independent, because it was also evident in leptin- (ob/ob) and leptin receptor deficient (db/db) mice and was paralleled with decreased food intake and increased energy expenditure in these mutant, obese animals. Such plasticity was also observed in other hypothalamic regions in response to high fat diet and fasting as well as in extrahypothalamic sites such as the midbrain and hippocampus altering reward associated behaviors and higher brain functions, including learning and memory. These observations promote the notion that synaptic plasticity is an important component of peripheral metabolic hormones' action on the brain. |
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Genomics of Obesity
1:30 PM-4:45 PM, Tuesday, August 21, 2007 BCEC -- 203, Oral
Biotechnology of Health and Wellness |