Subthalamic Nucleus Deep Brain Stimulation Does Not Modify the Functional Deficits or Axonopathy Induced by...

Area of Science:

• Neuroscience
• Neurology
• Molecular Biology

Background:

• Subthalamic nucleus deep brain stimulation (STN DBS) is known to protect dopaminergic neurons against certain toxins.
• Alpha-synuclein pathology is a hallmark of Parkinson's disease and related synucleinopathies.
• The efficacy of STN DBS in models with alpha-synuclein pathology remains to be fully elucidated.

Purpose of the Study:

• To investigate the neuroprotective effects of STN DBS in a rat model of Parkinson's disease with alpha-synuclein pathology.
• To determine if STN DBS can prevent dopaminergic neuron loss and motor deficits induced by alpha-synuclein overexpression.

Main Methods:

• Rats received unilateral intranigral injections of adeno-associated virus to overexpress human alpha-synuclein, creating a model of synucleinopathy.
• Following induction of pathology, rats underwent four weeks of STN DBS or sham stimulation.
• Behavioral tests (forelimb asymmetry) and histological analyses (dopaminergic neuron counts, striatal terminal density, p-rpS6 levels) were performed.

Main Results:

• Alpha-synuclein overexpression led to progressive forelimb asymmetry, loss of striatal dopaminergic terminals, and modest dopaminergic neuron loss.
• STN DBS did not protect against these alpha-synuclein-induced deficits.
• Forelimb asymmetry was exacerbated during STN DBS, suggesting impaired neurotransmission.

Conclusions:

• STN DBS does not offer neuroprotection in this model of alpha-synuclein overexpression.
• STN DBS may worsen motor deficits associated with alpha-synuclein pathology.
• Further research is needed to understand STN DBS's role in other synucleinopathy models.