Activation of neuropeptide FF neurons in the brainstem nucleus tractus solitarius following cardiovascular challenge and opiate withdrawal

Abstract

Neuropeptide FF (NPFF), a morphine modulatory peptide, is localized within discrete autonomic regions including the brainstem nucleus tractus solitarius (NTS) and the parabrachial nucleus (PBN). We investigated the activation of NPFF neurons in the NTS of rats induced by cardiovascular challenge and centrally generated opiate withdrawal. For hypotensive stimulation, we used systemic infusions of sodium nitroprusside (NP) or hemorrhage (HEM), and hypertension was achieved by intravenous phenylephrine (PHENYL) or angiotensin II (AII). In rats that received continuous intracerebroventricular injections of morphine, intraperitoneal injections of naloxone precipitated behavioural signs of opioid withdrawal. Activated NTS neurons were identified by using a combined immunohistochemistry for Fos and NPFF, and neurons projecting to the PBN were determined with a retrograde tracer. HEM, administration of vasoactive drugs, and opiate withdrawal produced a very robust activation of NTS neurons. In NP and HEM groups, 25.6+/-3.2% and 7.6+/-1.3% of NPFF neurons were activated, respectively. Lesser numbers of NPFF neurons were activated in the PHENYL (4.6+/-1.6%) and AII (2.4+/-0.8%) groups. However, following opiate withdrawal, virtually no Fos expression was observed in NPFF neurons. NPFF neurons activated during NP infusion constituted the largest number of cells projecting to the PBN. This study shows that NPFF neurons in NTS that project to the PBN respond selectively to NP as opposed to other cardiovascular challenges or opiate withdrawal. These data support an emerging and important role for NPFF in the context of central cardiovascular regulation.

Role of neuropeptide FF in central cardiovascular and neuroendocrine regulation

“…These include the prolactin-releasing peptide (PrRP) family (Hinuma et al, 1998), the family of neuropeptide FF (NPFF; and related peptides neuropeptide AF (NPAF), neuropeptide SF (NPSF), and neuropeptide VF (NPVF); Perry et al, 1997; Vilim et al, 1999; Bonini et al, 2000; Liu et al, 2001), human RFamide related peptides (hRFRPs; Hinuma et al, 2000; Fukusumi et al, 2001), metastin/kisspeptins (Ohtaki et al, 2001), and pyroglutamylated RFamide peptide (QRFP) (26RFa) family (Chartrel et al, 2003; Fukusumi et al, 2003). Of these, NPFF peptides and PrRP have been identified by our laboratory and others to play an important role in CNS regulation of cardiovascular function (Thiemermann et al, 1991; Allard et al, 1995; Jhamandas et al, 1998; Samson et al, 2000; Jhamandas and MacTavish, 2002). hRFRPs, which are encoded by a human gene, have a significant homology to the NPFF family of peptides and their receptors (Fukusumi et al, 2006).…”

Dynamic transcriptomic response to acute hypertension in the nucleus tractus solitarius

“…The data requirements of the present study necessitated development of novel microarray methods providing increased sensitivity to detect changes in the physiological range of neuronal gene regulation: 20 -80% (11,28,30). Further, the genes on the microarray are the full set of all genes for which functional annotation (LocusLink ID) was available at the time of array manufacture plus additional genes annotated as "similar to" genes in other organisms with neuronal specific functions.…”

“…Thus, the previous Fos studies imply that elevated baroreceptor afferent drive to the NTS may lead to gene regulatory responses of NTS neurons in the cvNTS. This suggestion is bolstered by additional studies showing that increased baroreceptor inputs regulate the gene expression in NTS for tyrosine hydroxylase (TH) and neuropeptide Y (NPY) neuropeptide genes among others (10,28). Interestingly, the dynamics were different for these two gene regulatory responses, with the TH gene showing a faster time course than the NPY gene response.…”

Daily voluntary exercise alters the cardiovascular response to hemorrhage in conscious male rats

“…Moreover, current evidence suggests that chronic exercise can affect many areas of the brain involved in autonomic control of AP and HR (Zhu, Gao et al 2004; Nelson, Juraska et al 2005; Bakos, Hlavacova et al 2007; Mueller 2007; Kleiber, Zheng et al 2008). Some of these same central sites have been identified to be involved in mediating autonomic changes during the different phases of severe HEM (Ward and Darlington 1987; Krukoff, MacTavish et al 1995; Krukoff, MacTavish et al 1997; Chan and Sawchenko 1998; Jhamandas, Harris et al 1998; Buller, Smith et al 1999; Kakiya, Arima et al 2000; Pelaez, Schreihofer et al 2002). This raises the possibility that exercise training may impact the body’s ability to withstand severe hemorrhage via a change in neuronal responsiveness of specific brain nuclei known to play a role in HEM.…”