한빛사논문
- 조회6,234
Abstract
Sang Ryong Kim PhD1, Xiqun Chen PhD1, Tinmarla F. Oo BS1, Tatyana Kareva BS1, Olga Yarygina BS1, Chuansong Wang PhD3, Matthew During MD3, Nikolai Kholodilov MD1, Robert E. Burke MD1,2,*
1Neurology and, Columbia University, New York, NY
2Pathology and Cell Biology, Columbia University, New York, NY
3Human Cancer Genetics Program, Ohio State University, Columbus, OH
Email: Robert E. Burke MD
*Correspondence: Robert E. Burke MD, Department of Neurology, Room 306, Black Building, Columbia University, 650 West 168th Street, New York, NY 10032
Abstract
Objective:
A prevailing concept in neuroscience has been that the adult mammalian central nervous system is incapable of restorative axon regeneration. Recent evidence, however, has suggested that reactivation of intrinsic cellular programs regulated by protein kinase B (Akt)/mammalian target of rapamycin (mTor) signaling may restore this ability.
Methods:
To assess this possibility in the brain, we have examined the ability of adenoassociated virus (AAV)-mediated transduction of dopaminergic neurons of the substantia nigra (SN) with constitutively active forms of the kinase Akt and the GTPase Ras homolog enriched in brain (Rheb) to induce regrowth of axons after they have been destroyed by neurotoxin lesion.
Results:
Both constitutively active myristoylated Akt and hRheb(S16H) induce regrowth of axons from dopaminergic neurons to their target, the striatum. Histological analysis demonstrates that these new axons achieve morphologically accurate reinnervation. In addition, functional reintegration into target circuitry is achieved, as indicated by partial behavioral recovery.
Interpretation:
We conclude that regrowth of axons within the adult nigrostriatal projection, a system that is prominently affected in Parkinson's disease, can be achieved by activation of Akt/mTor signaling in surviving endogenous mesencephalic dopaminergic neurons by viral vector transduction. ANN NEUROL 2011
논문정보
- Research article
- 2011년 07월 (BRIC 등록일 )
- 국외 연구진
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