Localization of nesfatin-1 neurons in the mouse brain and functional implication

Abstract

Nesfatin-1 reduces food intake when injected centrally in rodents. We recently described wide distribution of nucleobindin2 (NUCB2)/nesfatin-1 immunoreactivity in rat brain autonomic nuclei activated by various stressors. We used C57BL/6 mice to localize brain NUCB2/nesfatin-1 immunoreactivity and assessed activation of NUCB2/nesfatin 1 neurons after water avoidance stress (WAS). Gastric emptying of a non-nutrient liquid was also determined. NUCB2/nesfatin-1 immunoreactivity was detected in cortical areas including piriform, insular, cingulate and somatomotor cortices, the limbic system including amygdaloid nuclei, hippocampus and septum, the basal ganglia, bed nucleus of the stria terminalis, the thalamus including paraventricular and parafascicular nuclei, the hypothalamus including supraoptic, periventricular, paraventricular (PVN), arcuate nuclei and ventromedial and lateral hypothalamic areas. Intensely labeled NUCB2/nesfatin-1 neurons were detected in a previously undefined region which we named intermediate dorsomedial hypothalamus. In the brainstem, NUCB2/nesfatin-1 immunoreactivity was detected in the raphe nuclei, Edinger-Westphal nucleus, locus coeruleus (LC), lateral parabrachial nucleus, ventrolateral medulla (VLM) and dorsal vagal complex. WAS induced Fos expression in 35% of NUCB2/nesfatin-1-immunoreactive neurons in the PVN, 50% in the LC, 54% in the rostral raphe pallidus, 58% in the VLM, 39% in the middle part of the nucleus of the solitary tract (NTS) and 33% in the caudal NTS. Nesfatin-1 injected intracerebroventricularly significantly decreased gastric emptying. These data showed that NUCB2/nesfatin-1 immunoreactivity is distributed in mouse brain areas involved in the regulation of stress response and visceral functions activated by an acute psychological stressor suggesting that nesfatin-1 might play a role in the efferent component of the stress response.

Sex-specific differences in the dynamics of cocaine- and amphetamine-regulated transcript and nesfatin-1 expressions in the midbrain of depressed suicide victims vs. controls

“…Our data also resonate with recent interest in examining interactions between traditional mood substrates and pathways involved in the control of food intake and metabolism (for reviews see e.g. : Gomez-Pinilla, 2008;Krishnan and Nestler, 2008). There could be several candidate brain centres within which complex interactions between peripheral metabolic signals and centrally released regulators of feeding and arousal could underpin the general theme that an animal's metabolic status greatly influences mood and motivation.…”

“…the dysregulation of appetite in MDD. Such a mechanisms for central action for nesfatin/NUCB2 could be further supported by the fact that stress, a major trigger inducing appetite, affects nesfatin-1 neurons in several brain nuclei, including the EWcp (Goebel- Stengel et al, 2011;Stengel et al, 2009;Xu et al, 2010;Yoshida et al, 2010). In contrast, alterations in food intake (2-days fasting) do not effect nesfatin/NUCB2 expression in EWcp (Okere et al, 2010;Xu et al, 2009Xu et al, , 2010.…”

“…Recently significant interest has arisen in possible interactions between central mood substrates and circuitries involved in metabolism (Gomez-Pinilla, 2008;Krishnan and Nestler, 2008;Kuperman et al, 2010;McBriar, 2006;Shao et al, 2008). More specifically, several neuropeptides with a clear role in metabolism, such as leptin, ghrelin, orexin, neuropeptide Yand urocortin 3, produce clear anti-depressant-like responses (Eaton et al, 2007;Heilig, 2004;Kuperman et al, 2010;Lu, 2007;Lutter et al, 2008;Yamada et al, 2011), whereas e.g.…”

Is There any Association Between Nesfatin-1 and Generalized Anxiety Disorder?

“…Pre-clinical studies have provided supportive evidence that nesfatin-1 is involved in the pathogenesis of depression and anxiety 19,20 . Nesfatin-1 is observed in stress-related area such as the locus coeruleus and raphe nucleus 21 .…”

Role of nesfatin-1 in the metabolism of skeletal tissues

“…In fact, NUCB2/nesfatin-1 is abundantly expressed in several regions of the hypothalamus that play key roles in controlling food intake. It is now known that immunopositive reaction to NUCB2/nesfatin-1 also occurs in other areas, including the periventricular nucleus, Edinger-Westphal nucleus, dorsal nucleus of the vagus nerve, insular cortex, cerebellum as well as sympathetic and parasympathetic neurons of the spinal cord within the thoracic, lumbar, and sacral parts (6,14,16,20,24,31,38,62). Within neurons, nesfatin-1 occurs in conjunction with different neurotransmitters, including primarily melanin (MEL), cocaine-and amphetamine-regulated transcript (CART), proopiomelanocortin (POMC), α-melanocyte-stimulating hormone (α-MSH), growth hormone-releasing hormone (GHRH), thyrotropin-releasing hormone (TRH), corticotropin-releasing hormone (CRH), oxytocin (OT), vasopressin (AVP), neurotensin (NT), acetylocholine (Ach), and serotonin (SER) (6,12,14,16,31,34,39).…”