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Neuropeptide Y and α-melanocyte-stimulating hormone reciprocally regulate nesfatin-1 neurons in the paraventricular nucleus of the hypothalamus

Sedbazar, Udvala,*; Ayush, Enkh-Amara,*; Maejima, Yukoa; Yada, Toshihikoa,b

doi: 10.1097/WNR.0000000000000293
INTEGRATIVE SYSTEM
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Nesfatin-1 is an 82 amino acids peptide processed from its precursor nucleobindin-2 (NUCB2). Accumulating evidences have shown that the nesfatin-1/NUCB2 localized in the paraventricular nucleus (PVN) of the hypothalamus regulates food intake and energy metabolism. However, the factors that regulate nesfatin-1/NUCB2 neurons in PVN are less defined. In the hypothalamic feeding center, the second-order neurons in PVN are extensively projected by the first-order neurons in the arcuate nucleus (ARC), the representatives of which are orexigenic neuropeptide Y (NPY) and anorexigenic α-melanocyte-stimulating hormone (α-MSH) neurons. The present study explored whether NPY and α-MSH regulate the PVN nesfatin-1/NUCB2 neurons. This was achieved by cytosolic Ca2+ ([Ca2+]i) imaging, followed by nesfatin-1/NUCB2 immunostaining in single neurons isolated from PVN. The moderate increase in [Ca2+]i with 5 mM glucose was suppressed by NPY, but further increased by α-MSH in the PVN neurons that were shown to be immunoreactive to nesfatin-1/NUCB2. The majority (60%) of nesfatin-1/NUCB2 neurons in PVN responded to NPY and/or α-MSH. Confocal immunohistochemical images showed that both NPY and α-MSH neuronal terminals contacted nesfatin-1/NUCB2 neurons in PVN. These data show that NPY inhibits and α-MSH activates PVN nesfatin-1/NUCB2 neurons, presenting dual and reciprocal neuro-circuits from ARC to PVN, possibly contributing toward the balanced regulation of feeding.

aDepartment of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi

bDepartment of Development Physiology, Division of Adaptation Development, National Institute for Physiological Sciences, Okazaki, Aichi, Japan

* Udval Sedbazar and Enkh-Amar Ayush contributed equally to the writing of this article.

Correspondence to Toshihiko Yada, Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke, Tochigi 329-0498, Japan Tel: +81 285 58 7320; fax: +81 284 44 9962; e-mail: tyada@jichi.ac.jp

Received October 12, 2014

Accepted October 22, 2014

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins