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A dual role for AMP...
A dual role for AMP-activated protein kinase (AMPK) during neonatal hypoxic-ischaemic brain injury in mice
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Rousset, C. I. (författare)
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Leiper, F. C. (författare)
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Kichev, A. (författare)
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Gressens, P. (författare)
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Carling, D. (författare)
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- Hagberg, Henrik, 1955 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi,Institutionen för neurovetenskap och fysiologi,Institute of Clinical Sciences, Department of Obstetrics and Gynecology,Institute of Neuroscience and Physiology
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Thornton, C. (författare)
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(creator_code:org_t)
- 2015-02-24
- 2015
- Engelska.
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Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042. ; 133:2, s. 242-252
- Relaterad länk:
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https://onlinelibrar...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Perinatal hypoxic-ischaemic encephalopathy (HIE) occurs in 1-2 in every 1000 term infants and the devastating consequences range from cerebral palsy, epilepsy and neurological deficit to death. Cellular damage post insult occurs after a delay and is mediated by a secondary neural energy failure. AMP-activated protein kinase (AMPK) is a sensor of cellular stress resulting from ATP depletion and/or calcium dysregulation, hallmarks of the neuronal cell death observed after HIE. AMPK activation has been implicated in the models of adult ischaemic injury but, as yet, there have been no studies defining its role in neonatal asphyxia. Here, we find that in anin vivo model of neonatal hypoxia-ischaemic and in oxygen/glucose deprivation in neurons, there is pathological activationof the calcium/calmodulin-dependent protein kinase kinase (CaMKK)-AMPK1 signalling pathway. Pharmacological inhibition of AMPK during the insult promotes neuronal survival but, conversely, inhibiting AMPK activity prior to the insult sensitizes neurons, exacerbating cell death. Our data have pathological relevance for neonatal HIE as prior sensitization such as exposure to bacterial infection (reported to reduce AMPK activity) produces a significant increase in injury.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- AMPK
- hypoxia
- ischaemia
- neonatal
- oxygen-glucose deprivation
- MAGNETIC-RESONANCE-SPECTROSCOPY
- CHRONIC METFORMIN TREATMENT
- DEVELOPING
- RAT-BRAIN
- EXPERIMENTAL STROKE
- HUNTINGTONS-DISEASE
- MEDIATED
- ACTIVATION
- DOWN-REGULATION
- IMMATURE BRAIN
- NEURONS
- NEUROPROTECTION
- Biochemistry & Molecular Biology
- Neurosciences
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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