Tuberal Hypothalamic Neurons Secreting the Satiety Molecule Nesfatin-1 Are Critically Involved in Paradoxical REM Sleep HomeostasisReportar como inadecuado




Tuberal Hypothalamic Neurons Secreting the Satiety Molecule Nesfatin-1 Are Critically Involved in Paradoxical REM Sleep Homeostasis - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

The recently discovered Nesfatin-1 plays a role in appetite regulation as a satiety factor through hypothalamic leptin-independent mechanisms. Nesfatin-1 is co-expressed with Melanin-Concentrating Hormone MCH in neurons from the tuberal hypothalamic area THA which are recruited during sleep states, especially paradoxical sleep PS. To help decipher the contribution of this contingent of THA neurons to sleep regulatory mechanisms, we thus investigated in rats whether the co-factor Nesfatin-1 is also endowed with sleep-modulating properties. Here, we found that the disruption of the brain Nesfatin-1 signaling achieved by icv administration of Nesfatin-1 antiserum or antisense against the nucleobindin2 NUCB2 prohormone suppressed PS with little, if any alteration of slow wave sleep SWS. Further, the infusion of Nesfatin-1 antiserum after a selective PS deprivation, designed for elevating PS needs, severely prevented the ensuing expected PS recovery. Strengthening these pharmacological data, we finally demonstrated by using c-Fos as an index of neuronal activation that the recruitment of Nesfatin-1-immunoreactive neurons within THA is positively correlated to PS but not to SWS amounts experienced by rats prior to sacrifice. In conclusion, this work supports a functional contribution of the Nesfatin-1 signaling, operated by THA neurons, to PS regulatory mechanisms. We propose that these neurons, likely releasing MCH as a synergistic factor, constitute an appropriate lever by which the hypothalamus may integrate endogenous signals to adapt the ultradian rhythm and maintenance of PS in a manner dictated by homeostatic needs. This could be done through the inhibition of downstream targets comprised primarily of the local hypothalamic wake-active orexin- and histamine-containing neurons.



Autor: Sonia Jego, Denise Salvert, Leslie Renouard, Masatomo Mori, Romain Goutagny, Pierre-Hervé Luppi, Patrice Fort

Fuente: http://plos.srce.hr/



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