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@ARTICLE{Nacarkucuk:272509,
author = {Nacarkucuk, Efe and Bernis, Maria E. and Bremer,
Anna-Sophie and Grzelak, Kora and Zweyer, Margit and Maes,
Elke and Burkard, Hannah and Sabir, Hemmen},
title = {{N}europrotective {E}ffect of {M}elatonin in a {N}eonatal
{H}ypoxia–{I}schemia {R}at {M}odel {I}s {R}egulated by the
{AMPK}/m{TOR} {P}athway},
journal = {Journal of the American Heart Association},
volume = {13},
number = {19},
issn = {2047-9980},
address = {New York, NY},
publisher = {Association},
reportid = {DZNE-2024-01185},
pages = {e036054},
year = {2024},
abstract = {Melatonin has been shown to be neuroprotective in different
animal models of neonatal hypoxic-ischemic brain injury.
However, its exact molecular mechanism of action remains
unknown. Our aim was to prove melatonin's short- and
long-term neuroprotection and investigate its role on the
AMPK (AMP-activated protein kinase)/mTOR (mammalian target
of rapamycin) pathway following neonatal hypoxic-ischemic
brain injury.Seven-day-old Wistar rat pups were exposed to
hypoxia-ischemia, followed by melatonin or vehicle
treatment. Detailed analysis of the AMPK/mTOR/autophagy
pathway, short- and long-term neuroprotection, myelination,
and oligodendrogenesis was performed at different time
points. At 7 days after hypoxia-ischemia, melatonin-treated
animals showed a significant decrease in tissue loss,
increased oligodendrogenesis, and myelination. Long-term
neurobehavioral results showed significant motor improvement
following melatonin treatment. Molecular pathway analysis
showed a decrease in the AMPK expression, with a significant
increase at mTOR's downstream substrates, and a significant
decrease at the autophagy marker levels in the melatonin
group compared with the vehicle group.Melatonin treatment
reduced brain area loss and promoted oligodendrogenesis with
a clear improvement of motor function. We found that
melatonin associated neuroprotection is regulated via the
AMPK/mTOR/autophagy pathway. Considering the beneficial
effects of melatonin and the results of our study, melatonin
seems to be an optimal candidate for the treatment of
newborns with hypoxic-ischemic brain injury in high- as well
as in low- and middle-income countries.},
keywords = {Animals / Melatonin: pharmacology / Hypoxia-Ischemia,
Brain: metabolism / Hypoxia-Ischemia, Brain: drug therapy /
Hypoxia-Ischemia, Brain: pathology / TOR Serine-Threonine
Kinases: metabolism / Animals, Newborn / Rats, Wistar /
Neuroprotective Agents: pharmacology / Disease Models,
Animal / Signal Transduction: drug effects / AMP-Activated
Protein Kinases: metabolism / AMP-Activated Protein Kinases:
drug effects / Autophagy: drug effects / Oligodendroglia:
drug effects / Oligodendroglia: metabolism /
Oligodendroglia: pathology / Brain: drug effects / Brain:
metabolism / Brain: pathology / Rats / Behavior, Animal:
drug effects / AMPK/mTOR/autophagy (Other) / melatonin
(Other) / neonatal hypoxia–ischemia (Other) /
neuroprotection (Other) / rat (Other) / Melatonin (NLM
Chemicals) / TOR Serine-Threonine Kinases (NLM Chemicals) /
Neuroprotective Agents (NLM Chemicals) / mTOR protein, rat
(NLM Chemicals) / AMP-Activated Protein Kinases (NLM
Chemicals)},
cin = {AG Sabir / AG Salomoni},
ddc = {610},
cid = {I:(DE-2719)5000032 / I:(DE-2719)1013032},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC11681444},
pubmed = {pmid:39319465},
doi = {10.1161/JAHA.124.036054},
url = {https://pub.dzne.de/record/272509},
}