| Abstract No.: | C-E3171 |
| Country: | Canada |
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| Title: | NESFATIN-1 INHIBITS NPY NEURONS IN THE HYPOTHALAMIC ARCUATE NUCLEUS |
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| Authors/Affiliations: | 1 Christopher J. Price, 1 Alastair V. Ferguson
1 Queen's University, Department of Physiology, Kingston, ON, Canada |
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| Content: | Objectives: The novel peptide nesfatin-1, which is expressed in many hypothalamic nuclei, including the arcuate nucleus, acts as a satiety factor when injected intracerebroventricularly. However, the physiological basis for this effect is unknown. To help elucidate this we have examined how nesfatin-1 influences the excitability of different subtypes of neurons within the arcuate nucleus.
Materials and Methods: Whole cell current clamp recordings were performed on neurons in brain slices containing the arcuate nucleus and the response to bath applied nesfatin-1 determined. Neuronal phenotypes were identified using single cell RT-PCR using the DNase treated cytoplasm harvested from recorded neurons.
Results: Nesfatin-1 (10nM) had effects on the excitability of the majority of neurons tested (63%, n=84). Of these responsive neurons 62% hyperpolarized, with a mean amplitude of -9.6 ± 6.4 mV (n=33). The remaining responsive neurons depolarized with a mean amplitude of 6.9 ± 6.3 mV (n=20). Both depolarizations and hyperpolarizations were observed when slices were pretreated with the sodium channel blocker tetrodotoxin (1 μM). Of the neurons that were phenotyped using single cell RT-PCR, 17 were found to be NPY-expressing neurons. Of these, 9 hyperpolarized following nesfatin-1 exposure, while only 2 depolarized.
Conclusions: Nesfatin-1-inhibition of feeding was found to be mediated through the melanocortin-signaling system. Here we show that nesfatin-1 hyperpolarized orexigenic NPY neurons that are known to tonically inhibit anorexigenic pre-opiomelanocortin neurons within the arcuate nucleus. Nesfatin-1 would therefore negate this inhibition by NPY neurons and promote activation of neuronal pathways leading to the cessation of feeding.
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