Studies in Animals

In anesthetized adult rats, Fenik and Veasey studied the role of serotonin receptor subtypes in the excitation of neurons of the upper airway dilator muscles. The dose responses of agonists and antagonists injected into the hypoglossal nucleus were determined. An antagonist against serotonin receptor subtype 2A decreased intrinsic respiratory activity in the hypoglossal nerve by 61%, and suppressed serotonin excitation of the nerve. An antagonist against serotonin receptor subtype 2C decreased hypoglossal nerve activity by 17%, and suppressed the dose–response for the 2C agonist. Excitatory effects of the serotonin 2C agonist were of low magnitude and associated with rapid desensitization. An antagonist against serotonin receptor subtype 7 had no effect on either intrinsic activity or agonist responses. The authors conclude that serotonin 2A is the predominant excitatory serotonin receptor subtype of the hypoglossal motor neurons.

To determine whether prenatal hypoxia leads to sustained modifications in ventilatory control and impairs the ability to learn a spatial task, Gozal and coworkers exposed pregnant rats to intermittent hypoxia (10% oxygen concentration alternating with 21% oxygen every 90 seconds) or room air. At 5, 10, 15, and 30 days after delivery, newborn rats exposed to prenatal hypoxia had higher normoxic ventilation than did newborn rats exposed to prenatal room air. The peak ventilatory response to hypoxia at 5 days of age was depressed in rats exposed to prenatal hypoxia. Ventilatory equivalent (minute ventilation in relation to oxygen consumption) was decreased in rats exposed to prenatal hypoxia. The learning and memory of spatial tasks at one and four months was similar in rats exposed to prenatal hypoxia or normoxia. The authors conclude that gestational intermittent hypoxia leads to prolonged and irreversible alterations in respiratory control but does not produce obvious neurocognitive impairment.

Exposing an adult rat to intermittent hypoxia results in neurobehavioral impairment and increased apoptosis in the hippocampal CA1 region and cortex. In adult rats, Row and coworkers examined whether intermittent hypoxia induces lipid peroxidation in cortical tissue and whether the latter is associated with neurocognitive impairment. Exposing adult rats to intermittent hypoxia (alternating 90-second periods of 10% oxygen and 21% oxygen) caused impairment of the ability to learn a spatial task (in a water maze). Twice-daily treatment with an antioxidant (PNU-101033E) attenuated the impairment in spatial learning. The antioxidant also attenuated the increase in lipid peroxidation and isoprostane concentration associated with intermittent hypoxia. The authors conclude that exposure to intermittent hypoxia induces oxidative stress, which is associated with behavioral impairment.

Intermittent hypoxia during sleep induces significant neurobehavioral deficits in rats. To determine whether expression and activity of cyclogenase-2 (which is induced by cerebral ischemia) contributes to the development of neurobehavioral deficits, Li and coworkers examined the cortical regions of rat brain after exposure to either intermittent hypoxia (10% oxygen alternating with 21% oxygen every 90 seconds) or sustained hypoxia (10% oxygen). Intermittent hypoxia induced an increase in cyclooxygenase-2 protein and gene expression between the first and fourteenth day of exposure. Expression of the gene for cyclooxygenase-1 was not affected by hypoxia. Upregulation of cyclooxygenase-2 in response to intermittent hypoxia was associated with increased tissue levels of prostaglandin E₂, neuronal apoptosis, and neurobehavioral deficits. Selective inhibition of cyclooxygenase-2 with NS-398 attenuated the deficits in acquisition and retention of a spatial task (in a water maze) induced by intermittent hypoxia. The authors conclude that intermittent hypoxia induces upregulation and activation of cyclooxygenase-2 in rat cortex and that this enzyme may modulate the neurobehavioral deficits induced by chronic hypoxia.

Citations 1-4 of 4 total displayed.

Cyclooxygenase 2 and Intermittent Hypoxia-induced Spatial Deficits in the Rat

Richard C. Li, Barry W. Row, Evelyne Gozal, Leila Kheirandish, Qiang Fan, Kenneth R. Brittian, Shang Z. Guo, Leroy R. Sachleben, Jr., and David Gozal
Am. J. Respir. Crit. Care Med. 168: 469 -475. First published online as doi:10.1164/rccm.200211-1264OC [Abstract] [Full text]

Respiratory Effects of Gestational Intermittent Hypoxia in the Developing Rat

David Gozal, Stephen R. Reeves, Barry W. Row, Jennifer J. Neville, Shang Z. Guo, and Andrew J. Lipton
Am. J. Respir. Crit. Care Med. 167: 1540 -1547. First published online as doi:10.1164/rccm.200208-963OC [Abstract] [Full text]

Intermittent Hypoxia Is Associated with Oxidative Stress and Spatial Learning Deficits in the Rat

Barry W. Row, Rugao Liu, Wei Xu, Leila Kheirandish, and David Gozal
Am. J. Respir. Crit. Care Med. 167: 1548 -1553. First published online as doi:10.1164/rccm.200209-1050OC [Abstract] [Full text]

Pharmacological Characterization of Serotonergic Receptor Activity in the Hypoglossal Nucleus

Polina Fenik and Sigrid C. Veasey
Am. J. Respir. Crit. Care Med. 167: 563 -569. First published online as doi:10.1164/rccm.200202-107OC [Abstract] [Full text]

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