Distribution of the neuropeptide FF1 receptor (hFF1) in the human hypothalamus and surrounding basal forebrain structures: Immunohistochemical study

Abstract

Neuropeptides with C-terminal RFamide and their receptors NPFF1 (FF1) and NPFF2 (FF2) have been implicated in a wide variety of functions, including nociception and autonomic and neuroendocrine regulation. Recent studies indicate that the FF1, but not FF2, mRNA is highly expressed in the human hypothalamus. In the present study, localization of FF1 in the human hypothalamus and surrounding regions was studied immunohistochemically by using an antibody against human FF1 (hFF1). Brain sections from healthy 30-50-year-old individuals were used for hFF1 immunohistochemistry. The highest density of hFF1-stained cells was found in the posterior division of the bed nucleus of the stria terminalis and in the zona incerta. A moderate density of cells was observed in the perifornical nucleus, infundibular nucleus, tuberomammillary nucleus, and lateral tuberal nucleus. A lesser density was revealed in the dorsomedial hypothalamic nucleus, basal nucleus of Meynert, and anterior amygdaloid area. Only scattered hFF1 cells were found in the suprachiasmatic nucleus and hypothalamic paraventricular nucleus. hFF1 cells and fibers were absent in the supraoptic and mammillary nuclei. Single and double strands of hFF1-immunopositive punctate varicosities marked cellular processes of different caliber. The density of hFF1-immunostained fiber networks did not always coincide with that of hFF1-immunostained cells. hFF1 immunoreactivity was also found in the wall of blood vessels within most brain areas studied. Localization of hFF1 in discrete regions of the hypothalamus and extended amygdala may provide important insights into the role of amidated neuropeptides in central autonomic and neuroendocrine control in the human brain.

The human lateral tuberal nucleus: Immunohistochemical characterization and analogy to the rodent PV1-nucleus

“…To this end, the structures were subjected to an immunohistochemical analysis for a panel of reference neural markers. Somatostatin, and FF1 are recognized markers if the human LTN (Timmers et al, 1996;Goncharuk et al, 2004), whereas the calcium-binding protein parvalbumin is the typical marker of the rodent PV1-nucleus (hence its name) (Celio, 1990). Specimens were subjected to an immunohistochemical analysis not only for these markers but also for two other calcium-binding proteins, namely calretinin and calbindin, which also occur in the hypothalamus.…”

“…The presence of somatostatin and of the neuropeptide FF receptor FF1 let to speculations that it might be involved in the regulation of food intake and in the homeostasis of the neuroendocrine system (Timmers et al, 1996;Goncharuk et al, 2004;Dockray, 2004;Nicklous and Simansky, 2003).…”

“…It is a paradigm of neuroscience that the functional analysis of human brain areas is promoted and facilitated if homologous structures are known to exist in lower mammals. But in the case of the LTN, only primates appear to possess a similar structure (Fujii, 1982;Narkiewicy et al, 1994;Goncharuk et al, 2004). The occurrence of an LTN in rodents is controversial.…”

Cold-Induced Thermogenesis and Inflammation-Associated Cold-Seeking Behavior Are Represented by Different Dorsomedial Hypothalamic Sites: A Three-Dimensional Functional Topography Study in Conscious Rats

“…The limbic targets of NPFF-containing neurons are the septum, BNST, and several amygdalar subnuclei. The septum and BNST also have some of the highest densities of type-1 NPFF receptors in the rat and human brains (Bonini et al, 2000; Goncharuk et al, 2004). …”

G protein-coupled receptors in the hypothalamic paraventricular and supraoptic nuclei – serpentine gateways to neuroendocrine homeostasis

“…Some GPCRs appear to be preferentially expressed in the pPVN (e.g., consistent with regulating stress or autonomic responses), or mPVN (e.g., compatible with regulating water homeostasis or reproductive status) by either IHC and/or ISHH (pPVN: 5-HT 2C [118]; angiotensin AT 1A [245]; prolactin-releasing peptide PRRP [195] receptors; mPVN: chemokine CXCR4 [44]; neuromedin U NMU2 [260]; κ opioid [299] receptors). One GPCR (neuropeptide FF/neuropeptide AF NPFF1) seems to be PVN-specific in rats [103], although ir-NPFF1 fibers found just dorsal to the SON, as in humans [102], may project to the SON [143] and be responsible for the inhibitory effects of centrally administered NPFF on hypovolemia-induced VP secretion into the blood [10].…”