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.

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

Guatteo, Ezia
Investigation
;
2022

Abstract

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.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11367/108902
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact