No Detectable Effect on Visual Responses Using Functional MRI in a Rodent Model of α-Synuclein Expression

Area of Science:

• Neuroscience
• Biomarker Discovery
• Neurodegenerative Diseases

Background:

• Parkinson's disease (PD) diagnosis is often delayed, necessitating early biomarkers for effective treatment.
• Alpha-synuclein aggregation is a hallmark of PD, and its presence in the retina suggests potential visual biomarkers.
• Current diagnostic methods lack sensitivity for early-stage PD monitoring.

Purpose of the Study:

• To investigate the impact of alpha-synuclein expression on visual system function in a rat model.
• To determine if fMRI can detect alterations in visual pathway activity due to alpha-synuclein.
• To evaluate the potential of fMRI-based visual responses as an early biomarker for Parkinson's disease.

Main Methods:

• A unilateral rat model of Parkinson's disease was created using adeno-associated virus (AAV) to express human wild-type alpha-synuclein in the substantia nigra pars compacta.
• Functional magnetic resonance imaging (fMRI) was employed to measure blood oxygen level-dependent (BOLD) responses to light stimulation in the visual system.
• Motor function and postmortem immunohistochemistry were used to validate alpha-synuclein expression.

Main Results:

• Adeno-associated virus mediated expression of alpha-synuclein was successfully induced and validated in rats.
• Functional magnetic resonance imaging (fMRI) detected robust BOLD responses to light stimulation in the visual systems of both control and alpha-synuclein-expressing rats.
• No significant difference in functional activation of the visual system was observed between rats expressing alpha-synuclein and controls.

Conclusions:

• Alpha-synuclein expression in the rat substantia nigra pars compacta did not alter functional activation in the visual system.
• fMRI-based assessment of visual responses is unlikely to serve as a sensitive biomarker for early Parkinson's disease detection.
• Further research is needed to identify reliable early biomarkers for Parkinson's disease progression.