Identification of novel mouse genes conferring posthypoxic pauses.

Although central to the susceptibility of adult diseases characterized by abnormal rhythmogenesis, characterizing the genes involved is a challenge. We took advantage of the C57BL/6J (B6) trait of hypoxia-induced periodic breathing and its absence in the C57BL/6J-Chr 1(A/J)/NaJ chromosome substitution strain to test the feasibility of gene discovery for this abnormality. Beginning with a genetic and phenotypic analysis of an intercross study between these strains, we discovered three quantitative trait loci (QTLs) on mouse chromosome 1, with phenotypic effects.

Post-sigh breathing behavior and spontaneous pauses in the C57BL/6J (B6) mouse.

The purpose was to examine sighs and spontaneous pauses in regard to the stability of resting breathing in the B6 strain, compared to the A/J strain. A 5-HT1A receptor agonist (buspirone) and a chromosomal substitution strain (B6a1) were used to further alter breathing patterning. Ten-minute recordings of room air breathing were collected from unanaesthetized B6, A/J, and B6a1 mice.

Effects of buspirone on posthypoxic ventilatory behavior in the C57BL/6J and A/J mouse strains.

Buspirone, a partial agonist of the serotonergic 5-HT1A receptor, improves breathing irregularities in humans with Rett syndrome or brain stem injury. The purpose of this study was to examine whether buspirone alters posthypoxic ventilatory behavior in C57BL/6J (B6) and A/J mouse strains. Measurements of ventilatory behavior were collected from unanesthetized adult male mice (n=6 for each strain) using the plethysmographic method.

Alpha-melanocyte stimulating hormone and adrenocorticotropic hormone: an alternative approach when thinking about restless legs syndrome?

Alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH) possess properties suggesting that they may be involved in the pathogenesis of restless legs syndrome (RLS). We sought to determine if alpha-MSH and ACTH when administered centrally in rat recapitulate features reminiscent of RLS: increased activity, sleep fragmentation, and periodic movements during sleep. Rats were instrumented with electroencephalography, electromyography, and intracerebral cannulae and recorded for the measurement of sleep, periodic movements, and behavior following intracerebroventricular administration of alpha-MSH, ACTH, or saline.

Post-hypoxic unstable breathing in the C57BL/6J mouse: effects of acetazolamide.

We examined whether acetazolamide (ACZ), a carbonic anhydrase inhibitor, would alter post-hypoxic ventilatory behavior and periodic breathing in the C57BL/6J (B6) mouse. Experiments were performed with unanaesthetized, awake adult male B6 mice (n = 5, 2.5 months old, 21.

The effects of gender and age on REM-related sleep-disordered breathing.

Sleep disordered breathing occurring predominantly in rapid eye movement REM sleep (rapid-eye-movement-related sleep-disordered breathing, REM SDB) is present in 10 to 36% of patients undergoing polysomnography (PSG) for suspected obstructive sleep apnea (O'Connor et al. in Am J Respir Crit Care Med 161:1465-1472, 2000; Resta et al. in J Respir Medicine 99:91-96, 2005; Haba-Rubio et al.

Acetazolamide protects against posthypoxic unstable breathing in the C57BL/6J mouse.

Acetazolamide (Acz), a carbonic anhydrase inhibitor, is used to manage periodic breathing associated with altitude and with heart failure. We examined whether Acz would alter posthypoxic ventilatory behavior in the C57BL/6J (B6) mouse model of recurrent central apnea. Experiments were performed with unanesthetized, awake adult male B6 mice (n = 9), ventilatory behavior was measured using flow-through whole body plethysmography.

Domperidone and ventilatory behavior: Sprague-Dawley versus Brown Norway rats.

Domperidone, a dopamine D(2) receptor antagonist, is a tool for uncovering the tonic and dynamic effects of the peripheral dopaminergic system in unanesthestized animals. The hypothesis was that domperidone effects would vary between strains of the same species. Ventilatory behavior -- frequency and minute ventilation -- was measured by the plethysmographic method in unrestrained adult male Sprague-Dawley (SD: n=8) and Brown Norway (BN: n=8) rats before, during and after rapid transition to 100% O(2) after 5 min of 13% O(2)/3% CO(2).