Neuropathology of the Basal Ganglia in SNCA Transgenic Rat Model of Parkinson's Disease: Involvement of Parvalbuminergic Interneurons and Glial-Derived Neurotropic Factor

Parkinson's disease (PD) is a neurodegenerative disease characterized by the accumulation of alpha-synuclein, encoded by the SNCA gene. The main neuropathological hallmark of PD is the degeneration of dopaminergic neurons leading to striatal dopamine depletion. Trophic support by a neurotrophin called glial-derived neurotrophic factor (GDNF) is also lacking in PD. We performed immunohistochemical studies to investigate neuropathological changes in the basal ganglia of a rat transgenic model of PD overexpressing alfa-synuclein. We observed that neuronal loss also occurs in the dorsolateral part of the striatum in the advanced stages of the disease. Moreover, along with the degeneration of the medium spiny projection neurons, we found a dramatic loss of parvalbumin interneurons. A marked decrease in GDNF, which is produced by parvalbumin interneurons, was observed in the striatum and in the substantia nigra of these animals. This confirmed the involvement of the striatum in the pathophysiology of PD and the importance of GDNF in maintaining the health of the substantia nigra.

Automated summary

This study used immunohistochemical studies to investigate neuropathological changes in a rat transgenic model of Parkinson's disease (PD). It found that in the advanced stages of the disease, there was neuronal loss in the dorsolateral part of the striatum, along with a dramatic loss of parvalbumin interneurons. A marked decrease in the neurotrophic factor called glial-derived neurotrophic factor (GDNF) was also observed in the striatum and substantia nigra of these animals. This confirms the involvement of the striatum in PD pathophysiology and the importance of GDNF in maintaining the health of the substantia nigra.