title: Intermittent hypoxia promotes recovery of respiratory motor function in spinal cord-injured mice depleted of serotonin in the central nervous system.
abstract: We examined the effect of repeated daily exposure to intermittent hypoxia (IH) on the recovery of respiratory and limb motor function in mice genetically depleted of central nervous system serotonin. Electroencephalography, diaphragm activity, ventilation, core body temperature, and limb mobility were measured in spontaneously breathing wild-type (Tph2(+/+)) and tryptophan hydroxylase 2 knockout (Tph2(-/-)) mice. Following a C2 hemisection, the mice were exposed daily to IH (i.e., twelve 4-min episodes of 10% oxygen interspersed with 4-min normoxic periods followed by a 90-min end-recovery period) or normoxia (i.e., sham protocol, 21% oxygen) for 10 consecutive days. Diaphragm activity recovered to prehemisection levels in the Tph2(+/+) and Tph2(-/-) mice following exposure to IH but not normoxia [Tph2(+/+) 1.3 ± 0.2 (SE) vs. 0.3 ± 0.2; Tph2(-/-) 1.06 ± 0.1 vs. 0.3 ± 0.1, standardized to prehemisection values, P < 0.01]. Likewise, recovery of tidal volume and breathing frequency was evident, although breathing frequency values did not return to prehemisection levels within the time frame of the protocol. Partial recovery of limb motor function was also evident 2 wk after spinal cord hemisection. However, recovery was not dependent on IH or the presence of serotonin in the central nervous system. We conclude that IH promotes recovery of respiratory function but not basic motor tasks. Moreover, we conclude that spontaneous or treatment-induced recovery of respiratory and motor limb function is not dependent on serotonin in the central nervous system in a mouse model of spinal cord injury.
authors.affiliation: John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan; Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan;
authors.forename: Dragana
authors.initials: D
authors.lastname: Komnenov
authors.affiliation: John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan; Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan;
authors.forename: Julia Z
authors.initials: JZ
authors.lastname: Solarewicz
authors.affiliation: John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan; Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan;
authors.forename: Fareeza
authors.initials: F
authors.lastname: Afzal
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Kwaku D
authors.initials: KD
authors.lastname: Nantwi
authors.affiliation: John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan; Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan; and.
authors.forename: Donald M
authors.initials: DM
authors.lastname: Kuhn
authors.affiliation: John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan; Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan; Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan; jmateika@med.wayne.edu.
authors.forename: Jason H
authors.initials: JH
authors.lastname: Mateika
mesh_terms: D000818:Animals; D003964:Diaphragm / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010100:Oxygen / Q000378:metabolism* / Q000627:therapeutic use; D020127:Recovery of Function / Q000502:physiology*; D012120:Respiration Disorders / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy; D015656:Respiratory Mechanics; D012701:Serotonin / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000150:complications / Q000503:physiopathology* / Q000628:therapy
chemical_list: D012701:Serotonin; D010100:Oxygen
keywords: diaphragm muscle activity; non-rapid eye movement sleep; repeated daily intermittent hypoxia; respiratory plasticity; telemetry