Anatomical and functional reconstruction of the nigrostriatal pathway by intranigral transplants

Autor: Mohamed Jaber, Mickael Decressac, Stephan Besnard, Laetitia Prestoz, Afsaneh Gaillard, Isabelle Frappé, Pierre-Olivier Fernagut
Přispěvatelé: Institut de physiologie et biologie cellulaires (IPBC), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Laboratoire Mouvement Adaptation Cognition (MAC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CNRS, Université de Poitiers, France Parkinson (2003), Fondation de l'Avenir (2005 et 2006), Institut de France-Fondation NRJ (2005), Fondation de France (2007 et 2008), Région Poitou Charentes (2003 et 2006)
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Aging
Calbindins
Dopamine
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Nigrostriatal pathway
Mice
0302 clinical medicine
Mesencephalon
Neural Pathways
Neurons
0303 health sciences
Dopaminergic
Olfactory Bulb
Substantia Nigra
Ventral tegmental area
medicine.anatomical_structure
surgical procedures
operative
Neurology
Female
Thérapie cellulaire
medicine.drug
Tyrosine 3-Monooxygenase
Maladie de Parkinson
Green Fluorescent Proteins
Mice
Transgenic
Substantia nigra
Amélioration fonctionnelle
Motor Activity
Biology
lcsh:RC321-571
03 medical and health sciences
S100 Calcium Binding Protein G
Fetal Tissue Transplantation
Dopaminergic Cell
medicine
Animals
Brain Tissue Transplantation
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
030304 developmental biology
Dopamine transporter
Dopamine Plasma Membrane Transport Proteins
Corpus Striatum
Mice
Inbred C57BL
Transplantation
G Protein-Coupled Inwardly-Rectifying Potassium Channels
nervous system
Vesicular Monoamine Transport Proteins
biology.protein
Neuroscience
030217 neurology & neurosurgery
Zdroj: Neurobiology of Disease, Vol 35, Iss 3, Pp 477-488 (2009)
Neurobiology of Disease
Neurobiology of Disease, Elsevier, 2009, 35 (3), pp.477-488. ⟨10.1016/j.nbd.2009.07.003⟩
ISSN: 0969-9961
1095-953X
Popis: (IF : 4,37); International audience; The main transplantation strategy in Parkinson's disease has been to place dopaminergic grafts not in their ontogenic site, the substantia nigra, but in their target area, the striatum with contrasting results. Here we have used green fluorescent protein transgenic mouse embryos as donors of ventral mesencephalic cells for transplantation into the pre-lesioned substantia nigra of an adult wild-type host. This allows distinguishing the transplanted cells and their projections from those of the host. Grafted cells integrated within the host mesencephalon and expressed the dopaminergic markers tyrosine hydroxylase, vesicular monoamine transporter 2 and dopamine transporter. Most of the dopaminergic cells within the transplant expressed the substantia nigra marker Girk2 while a lesser proportion expressed the ventral tegmental area marker calbindin. Mesencephalic transplants developed projections through the medial forebrain bundle to the striatum, increased striatal dopamine levels and restored normal behavior. Interestingly, only mesencephalic transplants were able to restore the nigrostriatal projections as dopamine neurons originating from embryonic olfactory bulb transplants send projections only in the close vicinity of the transplantation site that did not reach the striatum. Our results show for the first time the ability of intranigral foetal dopaminergic neurons grafts to restore the damaged nigrostriatal pathway in adult mice. Together with our previous findings of efficient embryonic transplantation within the pre-lesioned adult motor cortex, these results demonstrate that the adult brain is permissive to specific and long distance axonal growth. They further open new avenues in cell transplantation therapies applied for the treatment of neurodegenerative disorders such as Parkinson's disease.
Databáze: OpenAIRE
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