Premotor parkinsonism models

Area of Science:

• Neuroscience
• Pathology
• Animal Models

Background:

• Parkinson's disease (PD) presents with non-motor symptoms preceding motor deficits.
• Olfactory dysfunction, REM sleep behavior disorder (RBD), and constipation are significant premotor symptoms.
• Investigating these symptoms in preclinical models is crucial for understanding early PD pathogenesis.

Purpose of the Study:

• To review premotor symptoms of Parkinson's disease.
• To evaluate the recapitulation of these symptoms in toxin- and gene-based animal models.
• To discuss the relevance of these models for understanding early PD mechanisms.

Main Methods:

• Review of existing literature on PD models.
• Analysis of studies investigating olfactory, sleep, and gastrointestinal symptoms in toxin- and gene-based models.
• Comparison of findings across different model systems.

Main Results:

• Altered olfactory discrimination is reproducible in both toxin- and gene-based models.
• Sleep alterations and RBD-like features are observed, particularly in toxin-based models and non-human primates.
• Gastrointestinal dysfunction, including reduced colonic motility and enteric α-synuclein accumulation, is replicated in both model types.

Conclusions:

• Toxin- and gene-based models effectively recapitulate key premotor symptoms of Parkinson's disease.
• These models offer valuable insights into the pathophysiological mechanisms underlying early PD.
• Further research using these models can elucidate disease progression and inform therapeutic strategies.