Delayed Therapeutic Administration of Melatonin Enhances Neuronal Survival Through AKT and MAPK Signaling Pathways Following Focal Brain Ischemia in Mice.
J Mol Neurosci
; 72(5): 994-1007, 2022 May.
Article
em En
| MEDLINE
| ID: mdl-35307786
ABSTRACT
Melatonin has a role in the cell survival signaling pathways as a candidate for secondary stroke prevention. Therefore, in the present study, the coordination of ipsilateral and contralateral hemispheres to evaluate delayed post-acute effect of melatonin was examined on recovery of the cell survival and apoptosis after stroke. Melatonin was administered (4 mg/kg/day) intraperitoneally for 45 days, starting 3 days after 30 min of middle cerebral artery occlusion. The genes and proteins related to the cell survival and apoptosis were investigated by immunofluorescence, western blotting, and RT-PCR techniques after behavioral experiments. Melatonin produced delayed neurological recovery by improving motor coordination on grip strength and rotarod tests. This neurological recovery was also reflected by high level of NeuN positive cells and low level of TUNEL-positive cells suggesting enhanced neuronal survival and reduced apoptosis at the fifty-fifth day of stroke. The increase of NGF, Nrp1, c-jun; activation of AKT; and dephosphorylation of ERK and JNK at the fifty-fifth day showed that cell survival and apoptosis signaling molecules compete to contribute to the remodeling of brain. Furthermore, an increase in the CREB and Atf-1 expressions suggested the melatonin's strong reformative effect on neuronal regeneration. The contralateral hemisphere was more active at the latter stages of the molecular and functional regeneration which provides a further proof of principle about melatonin's action on the promotion of brain plasticity and recovery after stroke.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Isquemia Encefálica
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Acidente Vascular Cerebral
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Melatonina
Limite:
Animals
Idioma:
En
Revista:
J Mol Neurosci
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Turquia
País de publicação:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA