TY - JOUR
T1 - Intermittent hypoxia training
T2 - Powerful, non-invasive cerebroprotection against ethanol withdrawal excitotoxicity
AU - Jung, Marianna E.
AU - Mallet, Robert T.
N1 - Funding Information:
This work was funded by research grants from the U.S. National Institute of Alcohol Abuse and Alcoholism [AA018747], the National Institute of Aging [AG053974], the National Institute of Neurological Disorders and Stroke [NS076975], UNTHSC Institute for Aging and Alzheimer's Disease Research, and UNTHSC Institute for Cardiovascular and Metabolic Diseases.
Funding Information:
This work was funded by research grants from the U.S. National Institute of Alcohol Abuse and Alcoholism [ AA018747 ], the National Institute of Aging [ AG053974 ], the National Institute of Neurological Disorders and Stroke [ NS076975 ], UNTHSC Institute for Aging and Alzheimer’s Disease Research , and UNTHSC Institute for Cardiovascular and Metabolic Diseases .
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2018/10
Y1 - 2018/10
N2 - Ethanol intoxication and withdrawal exact a devastating toll on the central nervous system. Abrupt ethanol withdrawal provokes massive release of the excitatory neurotransmitter glutamate, which over-activates its postsynaptic receptors, causing intense Ca2+ loading, p38 mitogen activated protein kinase activation and oxidative stress, culminating in ATP depletion, mitochondrial injury, amyloid β deposition and neuronal death. Collectively, these mechanisms produce neurocognitive and sensorimotor dysfunction that discourages continued abstinence. Although the brain is heavily dependent on blood-borne O2 to sustain its aerobic ATP production, brief, cyclic episodes of moderate hypoxia and reoxygenation, when judiciously applied over the course of days or weeks, evoke adaptations that protect the brain from ethanol withdrawal-induced glutamate excitotoxicity, mitochondrial damage, oxidative stress and amyloid β accumulation. This review summarizes evidence from ongoing preclinical research that demonstrates intermittent hypoxia training to be a potentially powerful yet non-invasive intervention capable of affording robust, sustained neuroprotection during ethanol withdrawal.
AB - Ethanol intoxication and withdrawal exact a devastating toll on the central nervous system. Abrupt ethanol withdrawal provokes massive release of the excitatory neurotransmitter glutamate, which over-activates its postsynaptic receptors, causing intense Ca2+ loading, p38 mitogen activated protein kinase activation and oxidative stress, culminating in ATP depletion, mitochondrial injury, amyloid β deposition and neuronal death. Collectively, these mechanisms produce neurocognitive and sensorimotor dysfunction that discourages continued abstinence. Although the brain is heavily dependent on blood-borne O2 to sustain its aerobic ATP production, brief, cyclic episodes of moderate hypoxia and reoxygenation, when judiciously applied over the course of days or weeks, evoke adaptations that protect the brain from ethanol withdrawal-induced glutamate excitotoxicity, mitochondrial damage, oxidative stress and amyloid β accumulation. This review summarizes evidence from ongoing preclinical research that demonstrates intermittent hypoxia training to be a potentially powerful yet non-invasive intervention capable of affording robust, sustained neuroprotection during ethanol withdrawal.
KW - Amyloid β
KW - Ethanol intoxication
KW - Excitotoxicity
KW - Glutamate
KW - Heat shock protein 25
KW - P38
KW - Presenilin 1
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=85030705118&partnerID=8YFLogxK
U2 - 10.1016/j.resp.2017.08.007
DO - 10.1016/j.resp.2017.08.007
M3 - Review article
C2 - 28811138
AN - SCOPUS:85030705118
SN - 1569-9048
VL - 256
SP - 67
EP - 78
JO - Respiratory Physiology and Neurobiology
JF - Respiratory Physiology and Neurobiology
ER -