c-<i>fos</i> Expression as a Marker of Central Cardiovascular Neurons

Abstract

Immunohistochemical detection of Fos, the protein product of the immediate-early gene c-fos, was evaluated as a functional marker of central neurons sensitive to a change of blood pressure/blood volume. Controlled hemorrhage and infusion of the hypotensive agent nitroprusside or hydralazine induced the appearance of Fos-immunoreactivity (Fos-IR) in several prominent groups of central neurons: the piriform cortex, bed nucleus of the stria terminalit, islands of Calleja, subfornical organ, central nucleus of the amygdala, parabrachial nucleus, supraoptic and paraventricular nuclei, pontine A5, locus ceruleus, ventrolateral medulla, the nucleus of the solitary tract, area postrema, and intermediolateral cell column in the spinal cord. Elevation of blood pressure by infusion of phenylephrine caused the appearance of Fos-IR in fewer groups of neurons: the bed nucleus of the stria terminalis, central nucleus of the amygdala, parabrachial nucleus, the nucleus of the solitary tract and area postrema. The differential distribution of Fos neurons in hypotensive versus hypertensive animals underscores the potential application of Fos as a metabolic marker in identifying a network of neurons responding to a specific cardiovascular challenge. Further, simultaneous characterization of the transmitter phenotype of Fos-containing neurons offers an additional advantage of this method over other conventional tract-tracing techniques.

Abdominal surgery activates nesfatin-1 immunoreactive brain nuclei in rats

“…Electrophysiological studies have shown that icv injection of CRF as well as microinjection around the LC region act on noradrenergic LC neurons [15, 44, 60] and LC neurons increase their activity dramatically in response to painful stimuli [22, 45]. Various stressors, for example restraint, tail shock, auditory and hypotensive stress increase extracellular norepinephrine levels in LC terminal regions [1, 10] and elevated levels of Fos mRNA and protein in the LC are induced in response to abdominal surgery, restraint, shock, hypotension, swim force, immune challenge, water avoidance stress and social stress [5, 6, 8, 12, 13, 18, 19, 24, 29, 32, 54] (present study). Taken together, these data suggest that the activation of nesfatin-1-ir neurons in the LC combined with LC-arising projections to CRF-containing neurons in the PVN which are also activated by abdominal surgery [6] (present study) and release of brain CRF contribute to the inhibition of gastric motor function and might be part of the factors leading to the development of postoperative ileus occurring after abdominal surgery (Fig.…”

The brain norepinephrine system, stress and cardiovascular vulnerability

“…The same stressors that initiate the HPA response to stress also activate the LC-NE system, including shock, auditory stress, immunological challenges, autonomic stressors, restraint and social stress. This has been determined using different endpoints of LC activity including NE turnover, NE release, LC neuronal activity, c-fos expression or tyrosine hydroxylase expression (Beck and Fibiger, 1995; Bonaz and Tache, 1994; Britton et al, 1992; Campeau and Watson, 1997; Cassens et al, 1981; Cassens et al, 1980; Chan and Sawchenko, 1995; Chang et al, 2000; Curtis et al, 2012; Dun et al, 1995; Duncan et al, 1993; Funk and Amir, 2000; Graham et al, 1995; Ishida et al, 2002; Kollack-Walker et al, 1997; Korf et al, 1973; Lacosta et al, 2000; Makino et al, 2002; Rusnak et al, 2001; Sabban and Kvetnansky, 2001; Smagin et al, 1994; Smith et al, 1992; Smith et al, 1991; Thierry et al, 1968; Valentino et al, 1991). The parallel activation of the HPA and LC-NE system would coordinate endocrine and cognitive limbs of the stress response (Valentino and Van Bockstaele, 2008).…”

Individual differences in the locus coeruleus-norepinephrine system: Relevance to stress-induced cardiovascular vulnerability

“…Various endpoints of LC activity have been used to verify its activation in response to stressors such as auditory stress, shock, immune system challenges, restraint and social stress and include expression of c-fos and tyrosine hydroxylase, neuronal activity of the LC, as well as NE turnover and release (Beck and Fibiger, 1995; Bonaz and Tache, 1994; Britton et al, 1992; Campeau and Watson, 1997; Cassens et al, 1981; Cassens et al, 1980; Chan and Sawchenko, 1995; Chang et al, 2000; Curtis et al, 2012; Dun et al, 1995; Duncan et al, 1993; Funk and Amir, 2000; Graham et al, 1995; Ishida et al, 2002; Kollack-Walker et al, 1997; Korf et al, 1973; Lacosta et al, 2000b; Makino et al, 2002; Rusnak et al, 2001; Sabban and Kvetnansky, 2001; Smagin et al, 1994; Smith et al, 1992; Smith et al, 1991; Thierry et al, 1968; Valentino et al, 1991b). Examining LC firing rate in both anesthetized and awake rats using electrophysiology has indicated that acute stress (including hypotensive stress, see below) and exposure to CRF can shift the LC firing rate from phasic to high tonic state, favoring cognitive flexibility and heightened arousal (Curtis et al, 2012; Valentino and Foote, 1987; Valentino and Foote, 1988; Valentino and Wehby, 1988; Zitnik et al, 2015).…”