Intermittent hypoxia conditioning protects mitochondrial cytochrome c oxidase of rat cerebellum from ethanol withdrawal stress

Ju, Xiaohua; Mallet, Robert T.; Downey, H. Fred; Metzger, Daniel; Jung, Marianna E.

doi:10.1152/japplphysiol.01428.2011

Cited by 27 publications

(35 citation statements)

References 54 publications

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“…3C). The increasing effect of EW on p38a in prefrontal cortex is consistent with previous observations that EW increases p38a in cerebellum (Jung et al, 2011;Ju et al, 2012). These results raise the possibility that EW-induced PS1 expression may depend on p38a.…”

Section: Resultssupporting

confidence: 91%

The Role of Presenilin-1 in the Excitotoxicity of Ethanol Withdrawal

Jung

Metzger

Das

2016

Journal of Pharmacology and Experimental Therapeutics

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Presenilin-1 (PS1) is a core component of g-secretase that is involved in neurodegeneration. We have previously shown that PS1 interacts with a mitogen-activated protein kinase [(MAPK) jun-NH2-terminal-kinase], and another MAPK (p38) is activated by ethanol withdrawal (EW), abrupt termination from chronic ethanol exposure. EW is excitotoxic in nature, induces glutamate upregulation, and provokes neuronal damage. Here, we explored a potential mechanistic pathway involving glutamate, p38 (p38a isozyme), and PS1 that may mediate EW-induced excitotoxic stress. We used the prefrontal cortex of male rats withdrawn from a chronic ethanol diet. Additionally, we used ethanol-withdrawn HT22 cells (mouse hippocampal) treated with the inhibitor of glutamate receptors [dizocilpine (MK-801)], p38aduring EW. Separately, ethanol-free HT22 cells were exposed to glutamate with or without SB203580 or DAPT. Protein levels, mRNA levels, and cell viability were assessed using immunoblotting, qualitative polymerase chain reaction, and calcein assay, respectively. The prefrontal cortex of ethanolwithdrawn rats or HT22 cells showed an increase in PS1 and p38a, which was attenuated by MK-801 and SB203580, but mimicked by glutamate treatment to ethanol-free HT22 cells. DAPT attenuated the toxic effect of EW or glutamate on HT22 cells. These results suggest that PS1 expression is triggered by glutamate through p38a, contributing to the excitotoxic stimulus of EW.

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Section: Resultssupporting

confidence: 91%

The Role of Presenilin-1 in the Excitotoxicity of Ethanol Withdrawal

Jung

Metzger

Das

2016

Journal of Pharmacology and Experimental Therapeutics

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“…In studies of alcohol withdrawal stress in rats, IHT attenuated oxidative damage to the brain and mitigated behavioral abnormalities. 99,199 In summary, there is robust evidence that IHT can impact many of the major VRF.…”

Section: Iht Reduces Vrfsmentioning

confidence: 98%

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease

Манухина

Downey

Shi

et al. 2016

Exp Biol Med (Maywood)

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Alzheimer's disease (AD) is a leading cause of death and disability among older adults. Modifiable vascular risk factors for AD (VRF) include obesity, hypertension, type 2 diabetes mellitus, sleep apnea, and metabolic syndrome. Here, interactions between cerebrovascular function and development of AD are reviewed, as are interventions to improve cerebral blood flow and reduce VRF. Atherosclerosis and small vessel cerebral disease impair metabolic regulation of cerebral blood flow and, along with microvascular rarefaction and altered trans-capillary exchange, create conditions favoring AD development. Although currently there are no definitive therapies for treatment or prevention of AD, reduction of VRFs lowers the risk for cognitive decline. There is increasing evidence that brief repeated exposures to moderate hypoxia, i.e. intermittent hypoxic training (IHT), improve cerebral vascular function and reduce VRFs including systemic hypertension, cardiac arrhythmias, and mental stress. In experimental AD, IHT nearly prevented endothelial dysfunction of both cerebral and extra-cerebral blood vessels, rarefaction of the brain vascular network, and the loss of neurons in the brain cortex. Associated with these vasoprotective effects, IHT improved memory and lessened AD pathology. IHT increases endothelial production of nitric oxide (NO), thereby increasing regional cerebral blood flow and augmenting the vaso-and neuroprotective effects of endothelial NO. On the other hand, in AD excessive production of NO in microglia, astrocytes, and cortical neurons generates neurotoxic peroxynitrite. IHT enhances storage of excessive NO in the form of S-nitrosothiols and dinitrosyl iron complexes. Oxidative stress plays a pivotal role in the pathogenesis of AD, and IHT reduces oxidative stress in a number of experimental pathologies. Beneficial effects of IHT in experimental neuropathologies other than AD, including dyscirculatory encephalopathy, ischemic stroke injury, audiogenic epilepsy, spinal cord injury, and alcohol withdrawal stress have also been reported. Further research on the potential benefits of IHT in AD and other brain pathologies is warranted.

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“…The rotarod behavioral test procedure was performed as previously described (Ju et al, 1985). The rotarod apparatus (AccuScan Instruments Inc., Columbus, OH) consisted of four cylinders that were mounted 35.5 cm above a cushion padded surface.…”

Section: Rotarod Assay Of Motor Performancementioning

confidence: 99%