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Ghrelin Promotes Cortical Neurites Growth in Late Stage After Oxygen-Glucose Deprivation/Reperfusion Injury.

Abstract
Acyl ghrelin, a novel brain-gut peptide, is an endogenous ligand for the growth hormone secretagogue receptor. Accumulated research data have shown that acyl ghrelin exercises a significant neuroprotective effect against cerebral ischemia/reperfusion (I/R) injury in animal models and in cultured neurons during the acute phase, usually, 1 day after cerebral ischemia. The chronic effects of acyl ghrelin 1 week after brain ischemia remain largely unknown. In this study, we explored the effects of acyl ghrelin on cultured organotypic brain slices and cortical neurons which were injured by oxygen-glucose deprivation/reperfusion(OGD/R) for 7 days. The underlying molecular mechanisms were deciphered based on label-free proteomic analysis. Acyl ghrelin treatment promoted neurite (axons and dendrites) growth and alleviated the neuronal damage in both cultured brain slices and neurons. Proteomic analysis showed that cell division control protein 42 (Cdc42) mediates the effects of acyl ghrelin on neurite growth. Acyl ghrelin stimulated the expression of Cdc42 and neurite growth in cultured neurons comparing with OGD/R group. Inhibition of Cdc42 attenuated the effects of acyl ghrelin. These results suggest that acyl ghrelin promotes neurite growth during the later stage after OGD/R injury via Cdc42. Our study suggests that acyl ghrelin may be promising to restore the neuronal structure in the late phase after stroke.
AuthorsJing Liu, Man Chen, Ruirui Dong, Changwei Sun, Shuo Li, Shigong Zhu
JournalJournal of molecular neuroscience : MN (J Mol Neurosci) Vol. 68 Issue 1 Pg. 29-37 (May 2019) ISSN: 1559-1166 [Electronic] United States
PMID30806968 (Publication Type: Journal Article)
Chemical References
  • Cdc42 protein, mouse
  • Ghrelin
  • Proteome
  • cdc42 GTP-Binding Protein
  • Glucose
  • Oxygen
Topics
  • Animals
  • Brain Ischemia (metabolism)
  • Cell Hypoxia
  • Cells, Cultured
  • Cerebral Cortex (cytology, drug effects, metabolism)
  • Ghrelin (metabolism, pharmacology)
  • Glucose (deficiency)
  • Mice
  • Mice, Inbred C57BL
  • Neuronal Outgrowth
  • Oxygen (metabolism)
  • Proteome (genetics, metabolism)
  • cdc42 GTP-Binding Protein (metabolism)

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