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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Obstructive sleep apnea (OSA) is a frequent medical condition characterized by intermittent hypoxia (IH) during sleep, and is associated with neurodegenerative changes in several brain regions along with learning deficits. We hypothesized that aging rats exposed to IH during sleep would be particularly susceptible. Young (3–4 months) and aging (20–22 months) Sprague–Dawley rats were therefore exposed to either room air or IH for 14 days. Learning and memory was assessed with a standard place-training version of the Morris water maze. Aging rats exposed to room air (RA) or IH displayed significant spatial learning impairments compared with similarly exposed young rats; furthermore, the decrements in performance between RA and IH were markedly greater in aging compared with young rats (p 〈 0.01), and coincided with the magnitude of IH-induced decreases in cyclic AMP response element binding (CREB) phosphorylation. Furthermore, decreases in proteasomal activity occurred in both young and aging rats exposed to IH, but were substantially greater in the latter (p 〈 0.001). Neuronal apoptosis, as shown by cleaved caspase 3 expression, was particularly increased in aging rats exposed to IH (p 〈 0.01 versus young rats exposed to IH). Collectively, these findings indicate unique vulnerability of the aging rodent brain to IH, which is reflected at least in part, by the more prominent decreases in CREB phosphorylation and a marked inability of the ubiquitin-proteasomal pathway to adequately clear degraded proteins.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Intermittent hypoxia (IH) during sleep, a hallmark of sleep apnea, is associated with neurobehavioral impairments, regional neurodegeneration and increased oxidative stress and inflammation in rodents. Platelet-activating factor (PAF) is an important mediator of both normal neural plasticity and brain injury. We report that mice deficient in the cell surface receptor for PAF (PAFR–/–), a bioactive mediator of oxidative stress and inflammation, are protected from the spatial reference learning deficits associated with IH. Furthermore, PAFR–/– exhibit attenuated elevations in inflammatory signaling (cyclo-oxygenase-2 and inducible nitric oxide synthase activities), degradation of the ubiquitin–proteasome pathway and apoptosis observed in wild-type littermates (PAFR+/+) exposed to IH. Collectively, these findings indicate that inflammatory signaling and neurobehavioral impairments induced by IH are mediated through PAF receptors.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Intermittent hypoxia (IH) during sleep, such as occurs in obstructive sleep apnea, leads to degenerative changes in the hippocampus, and is associated with spatial learning deficits in the adult rat. We report that in Sprague–Dawley rats the initial IH-induced impairments in spatial learning are followed by a partial functional recovery over time, despite continuing IH exposure. These functional changes coincide with initial decreases in basal neurogenesis as shown by the number of positively colabelled cells for BrdU and neurofilament in the dentate gyrus of the hippocampus, and are followed by increased expression of neuronal progenitors and mature neurons (nestin and BrdU-neurofilament positively labelled cells, respectively). In contrast, no changes occurred during the course of IH exposures in the expression of the synaptic proteins synaptophysin, SNAP25, and drebrin. Collectively, these findings indicate that the occurrence of IH during the lights on period results in a biphasic pattern of neurogenesis in the hippocampus of adult rats, and may account for the observed partial recovery of spatial function.
    Type of Medium: Electronic Resource
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