Hasanoglu Akbulut, N.Topal, G.Koc, C.Coskan, N.Salman, B.Cansev, M.Eyigor, O.2026-02-032026-02-0320250948-61431432-119Xhttps://doi.org/10.1007/s00418-025-02404-2https://hdl.handle.net/20.500.12428/34968Nesfatin-1, identified as an anorexigenic neuropeptide in the hypothalamus, is activated by glutamatergic agonists and innervated by excitatory and inhibitory neurons. The uridine nucleotide uridine diphosphate was recently identified as a novel regulator of feeding-related neurons. However, the activating effects of uridine and uridine nucleotides on anorexigenic NUCB2/nesfatin-1 neurons are unknown. In this study, the activating effects of intracerebroventricularly administered uridine or uridine nucleotides (UMP, UDP, UTP) on NUCB2/nesfatin-1 neurons localized in the supraoptic (SON), paraventricular (PVN), and periventricular (PeV) nuclei were determined using c-Fos immunohistochemistry. Results were evaluated as the percentage of the ratio of c-Fos-expressing (activated) NUCB2/nesfatin-1 neurons to all NUCB2/nesfatin-1 neurons. It was determined that centrally administered uridine, UMP, and UTP activated a statistically significant number of NUCB2/nesfatin-1 neurons in the SON, PVN, and PeV, compared with the saline group (p < 0.05). At the same time, the slight increase in the neuronal activation seen following UDP application was not found to be significant. The results of this study show that NUCB2/nesfatin-1 neurons respond to uridine and uridine nucleotides in the form of neuronal activation, possibly through pyrimidinergic neurotransmission.eninfo:eu-repo/semantics/closedAccessUridineUridine nucleotidesNUCB2Nesfatin-1Neuronal activationHypothalamic nucleiArticle163110.1007/s00418-025-02404-2Q2WOS:0015256915000012-s2.0-10501018114140624270Q2