Home > Publications Database > Neuroprotective Effect of Melatonin in a Neonatal Hypoxia–Ischemia Rat Model Is Regulated by the AMPK/mTOR Pathway > print

001     272509
005     20250127091515.0
024 7 _ |a pmc:PMC11681444
|2 pmc
024 7 _ |a 10.1161/JAHA.124.036054
|2 doi
024 7 _ |a altmetric:168836211
|2 altmetric
024 7 _ |a pmid:39319465
|2 pmid
037 _ _ |a DZNE-2024-01185
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Nacarkucuk, Efe
|0 P:(DE-2719)9002544
|b 0
|e First author
245 _ _ |a Neuroprotective Effect of Melatonin in a Neonatal Hypoxia–Ischemia Rat Model Is Regulated by the AMPK/mTOR Pathway
260 _ _ |a New York, NY
|c 2024
|b Association
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1729167939_2185
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a 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.
536 _ _ |a 352 - Disease Mechanisms (POF4-352)
|0 G:(DE-HGF)POF4-352
|c POF4-352
|f POF IV
|x 0
588 _ _ |a Dataset connected to CrossRef, Journals: pub.dzne.de
650 _ 7 |a AMPK/mTOR/autophagy
|2 Other
650 _ 7 |a melatonin
|2 Other
650 _ 7 |a neonatal hypoxia–ischemia
|2 Other
650 _ 7 |a neuroprotection
|2 Other
650 _ 7 |a rat
|2 Other
650 _ 7 |a Melatonin
|0 JL5DK93RCL
|2 NLM Chemicals
650 _ 7 |a TOR Serine-Threonine Kinases
|0 EC 2.7.11.1
|2 NLM Chemicals
650 _ 7 |a Neuroprotective Agents
|2 NLM Chemicals
650 _ 7 |a mTOR protein, rat
|0 EC 2.7.1.1
|2 NLM Chemicals
650 _ 7 |a AMP-Activated Protein Kinases
|0 EC 2.7.11.31
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Melatonin: pharmacology
|2 MeSH
650 _ 2 |a Hypoxia-Ischemia, Brain: metabolism
|2 MeSH
650 _ 2 |a Hypoxia-Ischemia, Brain: drug therapy
|2 MeSH
650 _ 2 |a Hypoxia-Ischemia, Brain: pathology
|2 MeSH
650 _ 2 |a TOR Serine-Threonine Kinases: metabolism
|2 MeSH
650 _ 2 |a Animals, Newborn
|2 MeSH
650 _ 2 |a Rats, Wistar
|2 MeSH
650 _ 2 |a Neuroprotective Agents: pharmacology
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Signal Transduction: drug effects
|2 MeSH
650 _ 2 |a AMP-Activated Protein Kinases: metabolism
|2 MeSH
650 _ 2 |a AMP-Activated Protein Kinases: drug effects
|2 MeSH
650 _ 2 |a Autophagy: drug effects
|2 MeSH
650 _ 2 |a Oligodendroglia: drug effects
|2 MeSH
650 _ 2 |a Oligodendroglia: metabolism
|2 MeSH
650 _ 2 |a Oligodendroglia: pathology
|2 MeSH
650 _ 2 |a Brain: drug effects
|2 MeSH
650 _ 2 |a Brain: metabolism
|2 MeSH
650 _ 2 |a Brain: pathology
|2 MeSH
650 _ 2 |a Rats
|2 MeSH
650 _ 2 |a Behavior, Animal: drug effects
|2 MeSH
700 1 _ |a Bernis, Maria E.
|0 P:(DE-2719)2810557
|b 1
|u dzne
700 1 _ |a Bremer, Anna-Sophie
|0 P:(DE-2719)9001591
|b 2
|u dzne
700 1 _ |a Grzelak, Kora
|0 P:(DE-2719)9003296
|b 3
|u dzne
700 1 _ |a Zweyer, Margit
|0 P:(DE-2719)9000835
|b 4
700 1 _ |a Maes, Elke
|0 P:(DE-2719)9001055
|b 5
|u dzne
700 1 _ |a Burkard, Hannah
|0 P:(DE-2719)9002524
|b 6
|u dzne
700 1 _ |a Sabir, Hemmen
|0 P:(DE-2719)9000732
|b 7
|e Last author
|u dzne
773 _ _ |a 10.1161/JAHA.124.036054
|g Vol. 13, no. 19, p. e036054
|0 PERI:(DE-600)2653953-6
|n 19
|p e036054
|t Journal of the American Heart Association
|v 13
|y 2024
|x 2047-9980
856 4 _ |y OpenAccess
|u https://pub.dzne.de/record/272509/files/DZNE-2024-01185.pdf
856 4 _ |y OpenAccess
|x pdfa
|u https://pub.dzne.de/record/272509/files/DZNE-2024-01185.pdf?subformat=pdfa
909 C O |o oai:pub.dzne.de:272509
|p openaire
|p open_access
|p VDB
|p driver
|p dnbdelivery
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 0
|6 P:(DE-2719)9002544
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 1
|6 P:(DE-2719)2810557
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 2
|6 P:(DE-2719)9001591
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 3
|6 P:(DE-2719)9003296
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 4
|6 P:(DE-2719)9000835
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 5
|6 P:(DE-2719)9001055
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 6
|6 P:(DE-2719)9002524
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 7
|6 P:(DE-2719)9000732
913 1 _ |a DE-HGF
|b Gesundheit
|l Neurodegenerative Diseases
|1 G:(DE-HGF)POF4-350
|0 G:(DE-HGF)POF4-352
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Disease Mechanisms
|x 0
914 1 _ |y 2024
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2023-08-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2023-08-29
915 _ _ |a Creative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0
|0 LIC:(DE-HGF)CCBYNCND4
|2 HGFVOC
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b J AM HEART ASSOC : 2022
|d 2023-08-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0501
|2 StatID
|b DOAJ Seal
|d 2022-11-30T16:55:33Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0500
|2 StatID
|b DOAJ
|d 2022-11-30T16:55:33Z
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2023-08-29
915 _ _ |a Fees
|0 StatID:(DE-HGF)0700
|2 StatID
|d 2023-08-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2023-08-29
915 _ _ |a OpenAccess
|0 StatID:(DE-HGF)0510
|2 StatID
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b DOAJ : Anonymous peer review
|d 2022-11-30T16:55:33Z
915 _ _ |a Article Processing Charges
|0 StatID:(DE-HGF)0561
|2 StatID
|d 2023-08-29
915 _ _ |a IF >= 5
|0 StatID:(DE-HGF)9905
|2 StatID
|b J AM HEART ASSOC : 2022
|d 2023-08-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2023-08-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0320
|2 StatID
|b PubMed Central
|d 2023-08-29
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2023-08-29
920 1 _ |0 I:(DE-2719)5000032
|k AG Sabir
|l Neonatal Neuroscience
|x 0
920 1 _ |0 I:(DE-2719)1013032
|k AG Salomoni
|l Nuclear Function in CNS Pathophysiology
|x 1
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a UNRESTRICTED
980 _ _ |a I:(DE-2719)5000032
980 _ _ |a I:(DE-2719)1013032
980 1 _ |a FullTexts

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21