Uridine and uridine nucleotides as novel regulators of NUCB2/nesfatin-1 neuron activation: an immunohistochemical study

Nesfatin-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.