Targeting Dramatically Activated Astrocytic Networks for Managing LID: a Target Validation Program

Objective/Rationale:
Astrocytes have long been regarded as passive partners of neurons in the central nervous system but this view has been challenged. Although astrocytes are now known to actively participate in information processing, their role in Parkinson’s disease and levodopa- induced dyskinesia pathological changes has remained almost untouched.

Project Description:
We hypothesize that the proliferation and activation of astrocytes in the parkinsonian and dyskinetic states permanently modify neurotransmission in the affected structures and play a role in both parkinsonian symptoms and aberrant response to levodopa in dyskinetic patients. We will here characterize both the morphological changes affecting astrocytes in these conditions as well as demonstrate, using pharmacological tools, that the astrocytes modulate neurotransmission in pathological states, thereby contributing to the manifestation of symptoms.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The project will reveal that astrocytes critically modulate cortico-striatal transmission, thereby offering opportunities for novel target identifications.

Anticipated Outcome:
The project is built to identify which elements of gliotransmission play a role (and if they play such a role) both in parkinsonian and dyskinetic symptoms. The study conveys the potential for moving the field forward in new pathophysiological and therapeutic directions.