Anatomical and functional reconstruction of the nigrostriatal pathway by intranigral transplants

Afsaneh Gaillard, Mickael Decressac, Isabelle Frappé, Pierre Olivier Fernagut, Laetitia Prestoz, Stephan Besnard, Mohamed Jaber
Neurobiology of Disease. 2009-09-01; 35(3): 477-488
DOI: 10.1016/j.nbd.2009.07.003

1. Neurobiol Dis. 2009 Sep;35(3):477-88. doi: 10.1016/j.nbd.2009.07.003. Epub
2009 Jul 17.

Anatomical and functional reconstruction of the nigrostriatal pathway by
intranigral transplants.

Gaillard A(1), Decressac M, Frappé I, Fernagut PO, Prestoz L, Besnard S, Jaber
M.

Author information:
(1)Institut de Physiologie et de Biologie Cellulaires, University of Poitiers,
CNRS, 40 avenue recteur Pineau, 86022 Poitiers Cedex, France.

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.