Dissociation between short-term increased graft survival and long-term functional improvements in Parkinsonian rats overexpressing glial cell line-derived neurotrophic factor.

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Fältnamn	Indikatorer	Metadata
000		04115naa a2200373 4500
001		oai:lup.lub.lu.se:cf7ed533-ec75-414b-a0c2-a875ff2717f4
003		SwePub
008		160401s2004 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://lup.lub.lu.se/record/1321622 URI
024	7	a https://doi.org/10.1111/j.1460-9568.2004.03770.x2 DOI
040		a (SwePub)lu
041		a engb eng
042		9 SwePub
072	7	a art2 swepub-publicationtype
072	7	a ref2 swepub-contenttype
100	1	a Georgievska, Biljanau Lund University,Lunds universitet,Neurobiologi,Forskargrupper vid Lunds universitet,Neurobiology,Lund University Research Groups4 aut0 (Swepub:lu)mphy-bge
245	1 0	a Dissociation between short-term increased graft survival and long-term functional improvements in Parkinsonian rats overexpressing glial cell line-derived neurotrophic factor.
264		c 2004-12-02
264	1	b Wiley,c 2004
338		a electronic2 rdacarrier
520		a The present study was designed to analyse whether continuous overexpression of glial cell line-derived neurotrophic factor (GDNF) in the striatum by a recombinant lentiviral vector can provide improved cell survival and additional long-term functional benefits after transplantation of fetal ventral mesencephalic cells in Parkinsonian rats. A four-site intrastriatal 6-hydroxydopamine lesion resulted in an 80–90% depletion of nigral dopamine cells and striatal fiber innervation, leading to stable motor impairments. Histological analysis performed at 4 weeks after grafting into the GDNF-overexpressing striatum revealed a twofold increase in the number of surviving tyrosine hydroxylase (TH)-positive cells, as compared with grafts placed in control (green fluorescent protein-overexpressing) animals. However, in animals that were allowed to survive for 6 months, the numbers of surviving TH-positive cells in the grafts were equal in both groups, suggesting that the cells initially protected at 4 weeks failed to survive despite the continued presence of GDNF. Although cell survival was similar in both grafted groups, the TH-positive fiber innervation density was lower in the GDNF-treated grafted animals (30% of normal) compared with animals with control grafts (55% of normal). The vesicular monoamine transporter-2-positive fiber density in the striatum, by contrast, was equal in both groups, suggesting that long-term GDNF overexpression induced a selective down-regulation of TH in the grafted dopamine neurons. Behavioral analysis in the long-term grafted animals showed that the control grafted animals improved their performance in spontaneous motor behaviors to approximately 50% of normal, whereas the GDNF treatment did not provide any additional recovery.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Neurovetenskaper0 (SwePub)301052 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Neurosciences0 (SwePub)301052 hsv//eng
700	1	a Carlsson, Thomasu Lund University,Lunds universitet,Neurobiologi,Forskargrupper vid Lunds universitet,Neurobiology,Lund University Research Groups4 aut0 (Swepub:lu)mphy-tka
700	1	a Lacar, Benjamin4 aut
700	1	a Winkler, Christianu Lund University,Lunds universitet,Neurobiologi,Forskargrupper vid Lunds universitet,Neurobiology,Lund University Research Groups4 aut0 (Swepub:lu)cell-cwi
700	1	a Kirik, Denizu Lund University,Lunds universitet,Neurobiologi,Forskargrupper vid Lunds universitet,Neurobiology,Lund University Research Groups4 aut0 (Swepub:lu)mphy-dki
710	2	a Neurobiologib Forskargrupper vid Lunds universitet4 org
773	0	t European Journal of Neuroscienced : Wileyg 20:11, s. 3121-3130q 20:11<3121-3130x 1460-9568x 0953-816X
856	4	u https://portal.research.lu.se/files/2611555/624283.pdfx primaryx freey FULLTEXT
856	4	u http://dx.doi.org/10.1111/j.1460-9568.2004.03770.xy FULLTEXT
856	4	u https://lup.lub.lu.se/search/files/2611555/624283.pdf
856	4 8	u https://lup.lub.lu.se/record/132162
856	4 8	u https://doi.org/10.1111/j.1460-9568.2004.03770.x

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Av författaren/redakt...: Georgievska, Bil ...; Carlsson, Thomas; Lacar, Benjamin; Winkler, Christi ...; Kirik, Deniz

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Neurovetenskaper

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Av lärosätet: Lunds universitet

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