Nucleobindin 2/nesfatin‐1 expression and colocalisation with neuropeptide Y and cocaine‐ and amphetamine‐regulated transcript in the human brainstem

Abstract

Feeding is a complex behaviour entailing elaborate interactions between forebrain, hypothalamic and brainstem neuronal circuits via multiple orexigenic and anorexigenic neuropeptides. Nucleobindin-2 (NUCB2)/nesfatin-1 is a negative regulator of food intake and body weight with a widespread distribution in rodent brainstem nuclei. However, its localisation pattern in the human brainstem is unknown. The present study aimed to explore NUCB2/nesfatin-1 immunoexpression in human brainstem nuclei and its possible correlation with body weight. Sections of human brainstem from 20 autopsy cases (13 males, seven females; eight normal weight, six overweight, six obese) were examined using immunohistochemistry and double immunofluorescence labelling. Strong immunoreactivity for NUCB2/nesfatin-1 was displayed in various brainstem areas, including the locus coeruleus, medial and lateral parabrachial nuclei, pontine nuclei, raphe nuclei, nucleus of the solitary tract, dorsal motor nucleus of vagus (10N), area postrema, hypoglossal nucleus, reticular formation, inferior olive, cuneate nucleus, and spinal trigeminal nucleus. NUCB2/nesfatin-1 was shown to extensively colocalise with neuropeptide Y and cocaine-and amphetamine-regulated transcript in the locus coeruleus, dorsal raphe nucleus and solitary tract. Interestingly, in the examined cases, NUCB2/nesfatin-1 protein expression was lower in obese than normal weight subjects in the solitary tract (P = 0.020). The findings of the present study provide neuroanatomical support for a role for NUCB2/ nesfatin-1 in feeding behaviour and energy balance. The widespread distribution of NUCB2/nesfatin-1 in the human brainstem nuclei may be indicative of its pleiotropic effects on autonomic, neuroendocrine and behavioural processes. In the solitary tract, a key integrator of energy status, altered neurochemistry may contribute to obesity. Further research is necessary to decipher human brainstem energy homeostasis circuitry, which, despite its importance, remains inadequately characterised.

Spexin and nesfatin-1-expressing neurons in the male human claustrum

“…The presence of nesfatin-1 in midbrain neurons and other sections of the brainstem does not seem surprising, considering the important role this neuropeptide plays in the hypothalamic control of energy homeostasis and metabolic activities. The executive stage of central, nesfatin-1-related regulation of food intake and other autonomic functions is carried out through brainstem centers including solitary tract nuclei (Psilopanagioti et al 2020). Against this background, the expression of nesfatin-1 in neurons of the vagus nerve (n. X) nuclei deserves special emphasis (Rupp and Stengel 2022).…”

Chemogenetic activation of endogenous arginine vasopressin exerts anorexigenic effects via central nesfatin-1/NucB2 pathway

“…Nesfatin-1/NucB2 immunoreactivity is co-expressed with neuropeptide Y and cocaine- and amphetamine-regulated transcript (CART) in the LC and DR in human [ 20 ]. Noradrenalin and serotonin (5-HT) producing neurons are localized in the LC and DR, respectively, and these monoamines are involved in wide variety of neuronal activity, including feeding.…”

Glucagon-like peptide-1 receptor in the human hypothalamus is associated with body mass index and colocalizes with the anorexigenic neuropeptide nucleobindin-2/nesfatin-1

“…Three to six hypothalamic sections per nucleus per case, taken at regular intervals throughout the rostrocaudal axis of each nucleus, were deparaffinized in a series of xylene and ethanol. Immunohistochemistry was performed as previously described [16, 20]. In brief, after blocking endogenous peroxidase activity, by incubating the sections in methanol containing 0.3 % H2O2 for 20 minutes, and performing antigen retrieval in citrate buffer (pH 6), sections were incubated overnight at 4 °C using a rabbit polyclonal anti-GLP-1R antibody (1:50; Origene, Rockville, MD, USA, TA336864).…”