Sökning: onr:"swepub:oai:lup.lub.lu.se:2457b4a6-1fc2-4714-98ab-ba548c792f83" >
Continuous low-leve...
Continuous low-level glial cell line-derived neurotrophic factor delivery using recombinant adeno-associated viral vectors provides neuroprotection and induces behavioral recovery in a primate model of Parkinson's disease
-
Eslamboli, A (författare)
-
- Georgievska, Biljana (författare)
- Lund University,Lunds universitet,Neurobiologi,Forskargrupper vid Lunds universitet,Neurobiology,Lund University Research Groups
-
Ridley, R M (författare)
-
visa fler...
-
Baker, H F (författare)
-
Muzyczka, N (författare)
-
Burger, C (författare)
-
Mandel, R J (författare)
-
Annett, L (författare)
-
- Kirik, Deniz (författare)
- Lund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Lund University Research Groups
-
visa färre...
-
(creator_code:org_t)
- 2005
- 2005
- Engelska.
-
Ingår i: The Journal of Neuroscience. - 1529-2401. ; 25:4, s. 769-777
- Relaterad länk:
-
http://dx.doi.org/10...
-
visa fler...
-
https://lup.lub.lu.s...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- The therapeutic potential of glial cell line-derived neurotrophic factor ( GDNF) for Parkinson's disease is likely to depend on sustained delivery of the appropriate amount to the target areas. Recombinant adeno-associated viral vectors ( rAAVs) expressing GDNF may be a suitable delivery system for this purpose. The aim of this study was to define a sustained level of GDNF that does not affect the function of the normal dopamine (DA) neurons but does provide anatomical and behavioral protection against an intrastriatal 6-hydroxydopamine (6-OHDA) lesion in the common marmoset. We found that unilateral intrastriatal injection of rAAV resulting in the expression of high levels of GDNF ( 14 ng/mg of tissue) in the striatum induced a substantial bilateral increase in tyrosine hydroxylase protein levels and activity as well as in DA turnover. Expression of low levels of GDNF (0.04 ng/mg of tissue), on the other hand, produced only minimal effects on DA synthesis and only on the injected side. In addition, the low level of GDNF provided similar to 85% protection of the nigral DA neurons and their projections to the striatum in the 6-OHDA-lesioned hemisphere. Furthermore, the anatomical protection was accompanied by a complete attenuation of sensorimotor neglect, head position bias, and amphetamine-induced rotation. We conclude that when delivered continuously, a low level of GDNF in the striatum ( approximately threefold above baseline) is sufficient to provide optimal functional outcome.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- adeno-associated virus
- gene therapy
- 6-hydroxydopamine
- GDNF
- dopamine
- monkey
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
Till lärosätets databas