Selective Glial Cell Line-Derived Neurotrophic Factor Production in Adult Dopaminergic Carotid Body CellsIn Situand after Intrastriatal Transplantation
Open Access
- 20 April 2005
- journal article
- research article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 25 (16), 4091-4098
- https://doi.org/10.1523/jneurosci.4312-04.2005
Abstract
Glial cell line-derived neurotrophic factor (GDNF) exerts a notable protective effect on dopaminergic neurons in rodent and primate models of Parkinson's disease (PD). The clinical applicability of this therapy is, however, hampered by the need of a durable and stable GDNF source allowing the safe and continuous delivery of the trophic factor into the brain parenchyma. Intrastriatal carotid body (CB) autografting is a neuroprotective therapy potentially useful in PD. It induces long-term recovery of parkinsonian animals through a trophic effect on nigrostriatal neurons and causes amelioration of symptoms in some PD patients. Moreover, the adult rodent CB has been shown to express GDNF. Here we show, using heterozygous GDNF/lacZ knock-out mice, that unexpectedly CB dopaminergic glomus, or type I, cells are the source of CB GDNF. Among the neural or paraneural cells tested, glomus cells are those that synthesize and release the highest amount of GDNF in the adult rodent (as measured by standard andin situELISA). Furthermore, GDNF expression by glomus cells is maintained after intrastriatal grafting and in CB of aged and parkinsonian 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated animals. Thus, glomus cells appear to be prototypical abundant sources of GDNF, ideally suited to be used as biological pumps for the endogenous delivery of trophic factors in PD and other neurodegenerative diseases.Keywords
This publication has 54 references indexed in Scilit:
- Co-transplantation of carotid body and ventral mesencephalic cells as an alternative approach towards functional restoration in 6-hydroxydopamine-lesioned rats: implications for Parkinson's diseaseJournal of Neurochemistry, 2004
- Localized striatal delivery of GDNF as a treatment for Parkinson diseaseNature Neuroscience, 2004
- Auto Transplants for Parkinson's Disease?Neuron, 1998
- Regulation of Astroglial-Derived Dopaminergic Neurotrophic Factors by Interleukin-1β in the Striatum of Young and Middle-Aged MiceExperimental Neurology, 1997
- Dopaminergic Neurons Protected from Degeneration by GDNF Gene TherapyScience, 1997
- Cellular expression of GDNF mRNA suggests multiple functions inside and outside the nervous systemCell and tissue research, 1996
- Functional recovery in parkinsonian monkeys treated with GDNFNature, 1996
- A single pulse of nerve growth factor triggers long-term neuronal excitability through sodium channel gene inductionNeuron, 1995
- GDNF: a Glial Cell Line-Derived Neurotrophic Factor for Midbrain Dopaminergic NeuronsScience, 1993
- Autotransplantation of the superior cervical ganglion into the brainJournal of Neurosurgery, 1988