Abstract
BackgroundThe human hypothalamus contains the neuropeptide FF (NPFF) neurochemical network. Animal experiments demonstrated that NPFF is implicated in the central cardiovascular regulation. We therefore studied expression of this peptide in the hypothalamus of individuals who suffered from essential hypertension (n = 8) and died suddenly due to acute myocardial infarction (AMI), and compared to that of healthy individuals (controls) (n = 6) who died abruptly due to mechanical trauma of the chest.MethodsThe frozen right part of the hypothalamus was cut coronally into serial sections of 20 μm thickness, and each tenth section was stained immunohistochemically using antibody against NPFF. The central section through each hypothalamic nucleus was characterized by the highest intensity of NPFF immunostaining and thus was chosen for quantitative densitometry.ResultsIn hypertensive patients, the area occupied by NPFF immunostained neuronal elements in the central sections through the suprachiasmatic nucleus (SCh), paraventricular hypothalamic nucleus (Pa), bed nucleus of the stria terminalis (BST), perinuclear zone (PNZ) of the supraoptic nucleus (SON), dorso- (DMH), ventromedial (VMH) nuclei, and perifornical nucleus (PeF) was dramatically decreased compared to controls, ranging about six times less in the VMH to 15 times less in the central part of the BST (BSTC). The NPFF innervation of both nonstained neuronal profiles and microvasculature was extremely poor in hypertensive patients compared to control.ConclusionsThe decreased NPFF expression in the hypothalamus of hypertensive patients might be a cause of impairment of its interaction with other neurochemical systems, and thereby might be involved in the pathogenesis of the disease.
Highlights
At first glance, neuropeptide FF (NPFF) neuronal elements were deemed to be distributed within various parts of the suprachiasmatic nucleus (SCh), further analysis revealed the density of the NPFF fibers in the medial (SChm) and lateral (SChl) parts of the SCh to be elevated compared to the central (SChc) part and even significantly more so when compared to that in the ventral (SChv) part of the nucleus that is partly embedded in the optic chiasm
Our observations concerning the distribution of hypothalamic NPFF in healthy individuals match those reported for human NPFF receptors (Goncharuk et al 2004; Goncharuk and Jhamandas 2008) and their respective mRNAs (Bonini et al 2000; Elshourbagy et al 2000)
In healthy individuals comprising the control group, neuronal NPFF cell bodies and the more numerous NPFF-expressing fibers are diffusely distributed throughout the rostro-caudal axis of the hypothalamus compared to the rat, which reflects well-known differences in segregation of homological hypothalamic nuclei between two species (Koutcherov et al 2000; Swaab 2003)
Summary
Neuropeptide FF (NPFF), a member of evolutionary highly conserved family of amidated neuropeptides (Yang et al 1985; Perry et al 1997; Nichols 2003; Lopez-Vera et al 2008), is involved in central regulation of a variety of physiological functions including food intake (Sunter et al 2001; Nicklous and Simansky 2003), fluid balance (Arima et al 1996; Sunter et al 2001), and nociception (Yang et al 2008). Conclusions: The decreased NPFF expression in the hypothalamus of hypertensive patients might be a cause of impairment of its interaction with other neurochemical systems, and thereby might be involved in the pathogenesis of the disease
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