Capacity of Neurotrophic Factors of the GDNF Family in Supporting the Survival of Dopaminergic Neurons in the Central Nervous System of the Aging Mouse

Abstract

Dopaminergic neurons of the substantia nigra are vital for proper motor function. The Glial cell line-derived neurotrophic factor (GDNF) family of neurotrophic factors have been shown to promote the survival of dopaminergic neurons both in vitro and in vivo. GDNF and its related factor neurturin have both been trialled as a therapy for Parkinson’s patients for which degeneration of dopaminergic neurons is hallmark pathology. However, GDNF and neurturin are not required for proper development of dopaminergic neurons. Knockout of the GDNF gene in mice causes improper formation of the enteric nervous and kidneys causing death shortly after birth but does not cause any changes in dopaminergic phenotype. Knockout of the neurturin gene is non-lethal but causes abnormalities in enteric, parasympathetic and sensory neurons. No abnormalities in the brain of neurturin knockout have been reported however very little work has been done in this area. It appears that these two neurotrophic factors are not required for successful dopaminergic development.