Parkinsonian phenotypes induced by Synphilin-1 expression are differentially contributed by serotonergic and dopaminergic circuits and suppressed by nicotine treatment

PLoS One. 2023 Mar 1;18(3):e0282348. doi: 10.1371/journal.pone.0282348. eCollection 2023.

Abstract

Synphilin-1 is a protein encoded by the human SNCAIP gene whose function has yet to be fully understood. However, it has been linked to familial Parkinson's disease (PD). Synphilin-1 is a major component of the Lewy bodies found in neurons in the substantia nigra pars compacta of PD patients. Synphilin-1 expression in serotonergic and/or dopaminergic neurons of Drosophila melanogaster induces neurodegeneration, as well as motor and non-motor PD like symptoms. In this work, we examined the contribution of the serotonergic and dopaminergic circuits in the development of PD-like phenotypes. We found that olfactory and visual symptoms are majorly contributed by the serotonergic system, and that motor symptoms and reduction in survival are mainly contributed by the dopaminergic system. Chronic nicotine treatment was able to suppress several of these symptoms. These results indicate that both the serotonergic and dopaminergic systems contribute to different aspects of PD symptomatology and that nicotine has beneficial effects on specific symptoms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopamine
  • Dopaminergic Neurons
  • Drosophila melanogaster
  • Humans
  • Nerve Tissue Proteins* / genetics
  • Nicotine* / pharmacology
  • Parkinsonian Disorders* / genetics
  • Phenotype

Substances

  • Dopamine
  • Nicotine
  • SNCAIP protein, human
  • Nerve Tissue Proteins

Grants and funding

This work was supported by the Consejo Nacional de Ciencia y Tecnología (CONACyT), grant number 255478 and by Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México (DGAPA-PAPIIT) grant number IN206517) ER was the recipient of the grants. AC received fellowships (446128) from CONACYT, PAEP-UNAM and Alianza del Pacífico- AGCID. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.