Human fetal dopamine neurons grafted in a rat model of Parkinson's disease : immunological aspects, spontaneous and drug-induced behaviour, and dopamine release

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Fältnamn	Indikatorer	Metadata
000		05498naa a2200577 4500
001		oai:lup.lub.lu.se:2c1fb430-acd1-48c7-abda-25cf692b15e1
003		SwePub
008		170419s1988 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://lup.lub.lu.se/record/2c1fb430-acd1-48c7-abda-25cf692b15e12 URI
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 Brundin, Patriku Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine4 aut0 (Swepub:lu)mphy-pbr
245	1 0	a Human fetal dopamine neurons grafted in a rat model of Parkinson's disease : immunological aspects, spontaneous and drug-induced behaviour, and dopamine release
264	1	c 1988
300		a 17 s.
520		a We have used a rat model of Parkinson's disease (PD) to address issues of importance for a future clinical application of dopamine (DA) neuron grafting in patients with PD. Human mesencephalic DA neurons, obtained from 6.5-8 week old fetuses, were found to survive intracerebral cell suspension xenografting to the striatum of rats immunosuppressed with Cyclosporin A. The grafts produced an extensive new DA-containing terminal network in the previously denervated caudate-putamen, and they normalized amphetamine-induced, apomorphine-induced and spontaneous motor asymmetry in rats with unilateral lesions of the mesostriatal DA pathway. Grafts from an 11.5-week old donor exhibited a lower survival rate and smaller functional effects. As assessed with the intracerebral dialysis technique the grafted DA neurons were found to restore spontaneous DA release in the reinnervated host striatum to normal levels. The neurons responded with large increases in extracellular striatal DA levels after the intrastriatal administration of the DA-releasing agent d-amphetamine and the DA-reuptake blocker nomifensine, although not to the same extent as seen in striata with an intact mesostriatal DA system. DA fiber outgrowth from the grafts was dependent on the localization of the graft tissue. Thus, grafts located within the striatum gave rise to an extensive axonal network throughout the whole host striatum, whereas grafted DA neurons localized in the neocortex had their outgrowing fibers confined within the grafts themselves. In contrast to the good graft survival and behavioural effects obtained in immunosuppressed rats, there was no survival, or behavioural effects, of human DA neurons implanted in rats that did not receive immunosuppression. In addition, we found that all the graft recipients were immunized, having formed antibodies against antigens present on human T-cells. This supports the notion that the human neurons grafted to the non-immunosuppressed rats underwent immunological rejection. Based on an estimation of the survival rate and extent of fiber outgrowth from the grafted human fetal DA neurons, we suggest that DA neurons that can be obtained from one fetus may be sufficient to restore significant DA neurotransmission unilaterally, in one putamen, in an immunosuppressed PD patient.
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
653		a Amphetamine
653		a Animals
653		a Antibodies
653		a Apomorphine
653		a Behavior, Animal
653		a Brain
653		a Dialysis
653		a Dopamine
653		a Female
653		a Fetus
653		a Graft Survival
653		a Humans
653		a Immunosuppression
653		a Neurons
653		a Parkinson Disease
653		a Rats
653		a Rats, Inbred Strains
653		a Transplantation, Heterologous
653		a Journal Article
653		a Research Support, Non-U.S. Gov't
700	1	a Strecker, R Eu Lund University4 aut
700	1	a Widner, Hu Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Regeneration in Movement Disorders,Forskargrupper vid Lunds universitet,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups4 aut0 (Swepub:lu)mphy-hwi
700	1	a Clarke, D Ju University of Oxford4 aut
700	1	a Nilsson, O Gu Lund University4 aut0 (Swepub:lu)lub-oni
700	1	a Åstedt, Bu Lund University4 aut
700	1	a Lindvall, Ou Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurogenes och Cellterapi,Forskargrupper vid Lunds universitet,Stem Cells & Restorative Neurology,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Neurogenesis and cell therapy,Lund University Research Groups4 aut0 (Swepub:lu)neur-oli
700	1	a Björklund, Au Lund University,Lunds universitet,Neurobiologi,Forskargrupper vid Lunds universitet,Neurobiology,Lund University Research Groups4 aut0 (Swepub:lu)mphy-abj
710	2	a Institutionen för experimentell medicinsk vetenskapb Medicinska fakulteten4 org
773	0	t Experimental Brain Researchg 70:1, s. 192-208q 70:1<192-208x 0014-4819
856	4 8	u https://lup.lub.lu.se/record/2c1fb430-acd1-48c7-abda-25cf692b15e1

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Av författaren/redakt...: Brundin, Patrik; Strecker, R E; Widner, H; Clarke, D J; Nilsson, O G; Åstedt, B; visa fler...; Lindvall, O; Björklund, A; visa färre...

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