title: Decreased CSF pH at ventral brain stem induces widespread c-Fos immunoreactivity in rat brain neurons.
abstract: Physiological evidence has indicated that central respiratory chemosensitivity may be ascribed to neurons located at the ventral medullary surface (VMS); however, in recent years, multiple sites have been proposed. Because c-Fos immunoreactivity is presumed to identify primary cells as well as second- and third-order cells that are activated by a particular stimulus, we hypothesized that activation of VMS cells using a known adequate respiratory stimulus, H(+), would induce production of c-Fos in cells that participate in the central pH-sensitive respiratory chemoreflex loop. In this study, stimulation of rostral and caudal VMS respiratory chemosensitive sites in chloralose-urethane-anesthetized rats with acidic (pH 7.2) mock cerebrospinal fluid induced c-Fos protein immunoreactivity in widespread brain sites, such as VMS, ventral pontine surface, retrotrapezoid, medial and lateral parabrachial, lateral reticular nuclei, cranial nerves VII and X nuclei, A(1) and C(1) areas, area postrema, locus coeruleus, and paragigantocellular nuclei. At the hypothalamus, the c-Fos reaction product was seen in the dorsomedial, lateral hypothalamic, supraoptic, and periventricular nuclei. These results suggest that 1) multiple c-Fos-positive brain stem and hypothalamic structures may represent part of a neuronal network responsive to cerebrospinal fluid pH changes at the VMS, and 2) VMS pH-sensitive neurons project to widespread regions in the brain stem and hypothalamus that include respiratory and cardiovascular control sites.
authors.affiliation: Department of Physiology, College of Medicine, Howard University, Washington, District of Columbia 20059, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Douglas
authors.forename: C O
authors.initials: CO
authors.lastname: Trouth
authors.forename: S D
authors.initials: SD
authors.lastname: James
authors.forename: L M
authors.initials: LM
authors.lastname: Sexcius
authors.forename: P
authors.initials: P
authors.lastname: Kc
authors.forename: O
authors.initials: O
authors.lastname: Dehkordi
authors.forename: E R
authors.initials: ER
authors.lastname: Valladares
authors.forename: J C
authors.initials: JC
authors.lastname: McKenzie
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D002628:Chemoreceptor Cells / Q000502:physiology*; D015870:Gene Expression; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D008526:Medulla Oblongata / Q000033:anatomy & histology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016760:Proto-Oncogene Proteins c-fos