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PMID: 10751440 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Akt/protein kinase B prevents injury-induced motoneuron death and accelerates axonal regeneration.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 20 ·No. 8 ·2000-04-15 ·Pages 2875-86

Namikawa K, Honma M, Abe K, Takeda M, Mansur K, Obata T, Miwa A, Okado H, Kiyama H

Abstract

Motoneurons require neurotrophic factors for their survival and axonal projection during development, as well as nerve regeneration. By using the axotomy-induced neuronal death paradigm and adenovirus-mediated gene transfer, we attempted to gain insight into the functional significances of major growth factor receptor downstream cascades, Ras-extracellular signal-regulated kinase (Ras-ERK) pathway and phosphatidylinositol-3 kinase-Akt (PI3K-Akt) pathway. After neonatal hypoglossal nerve transection, the constitutively active Akt-overexpressing neurons could survive as well as those overexpressing Bcl-2, whereas the constitutively active ERK kinase (MEK)-overexpressing ones failed to survive. A dominant negative Akt experiment demonstrated that inhibition of Akt pathway hastened axotomy-induced neuronal death in the neonate. In addition, the dominant active Akt-overexpressing adult hypoglossal neurons showed accelerated axonal regeneration after axotomy. These results suggest that Akt plays dual roles in motoneuronal survival and nerve regeneration in vivo and that PI3K-Akt pathway is probably more vital in neuronal survival after injury than Ras-ERK pathway.

MeSH Terms
Animals Animals, Newborn Axotomy Cell Death/physiology Enzyme Activation Gene Transfer Techniques Genetic Vectors/physiology Hypoglossal Nerve/physiology Hypoglossal Nerve Injuries Motor Neurons/physiology Nerve Regeneration/physiology Neurites/physiology PC12 Cells Phosphatidylinositol 3-Kinases/metabolism Protein Serine-Threonine Kinases Proto-Oncogene Proteins/physiology Proto-Oncogene Proteins c-akt Rats
Chemicals
Proto-Oncogene Proteins Akt1 protein, rat Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-akt
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Namikawa K
Department of Anatomy, Asahikawa Medical College, Asahikawa, Hokkaido, 078-8510 Japan.
Honma M
Abe K
Takeda M
Mansur K
Obata T
Miwa A
Okado H
Kiyama H
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2000-04-15
Pages
2875-86
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6772200
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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