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Astrocyte Responses Influence Local Effects of Whole-Brain Magnetic Stimulation in Parkinsonian Rats
Giuseppina Natale1, Micol Colella2, Maria De Carluccio1,3
1Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy.
Movement Disorders : Official Journal of the Movement Disorder Society
|September 13, 2023
Summary
Intermittent theta-burst stimulation (iTBS) improves motor function in Parkinson's disease models by modulating astrocyte function and glutamate transport. This noninvasive brain stimulation shows promise for Parkinson's disease treatment.
Area of Science:
- Neuroscience
- Neurodegenerative Diseases
- Brain Stimulation
Background:
- Excessive striatal glutamate transmission contributes to Parkinson's disease (PD) progression.
- Astrocytes regulate glutamate homeostasis via glutamate-aspartate transporter (GLAST), which is altered in PD.
- Intermittent theta-burst stimulation (iTBS) offers neuromodulatory effects and functional recovery in experimental parkinsonism.
Purpose of the Study:
- To investigate the regional- and cell-specific effects of acute iTBS on glial functions in PD.
- To test the hypothesis that iTBS modulates astrocyte function to rescue striatal glutamatergic transmission.
Main Methods:
- Utilized 6-hydroxydopamine-lesioned rats exposed to acute iTBS.
- Employed a biophysical computational model to predict responsive brain areas.
- Assessed iTBS effects on glial cells and motor behavior using molecular, morphological analyses, CatWalk, and Stepping tests.
Main Results:
- iTBS induced c-FOS activation in the hippocampus, cerebellum, and striatum, as predicted by the model.
- The striatum showed astrocyte-specific morphological and molecular changes, reduced phospho-CREB, and restored GLAST levels.
- Striatal-dependent motor performances were significantly improved following iTBS.
Conclusions:
- iTBS exerts previously unrecognized effects on astrocytes, enhancing understanding of TMS-mediated functional recovery mechanisms.
- Numerical dosimetry data, validated by biological findings, provide a predictive framework for electric-field induction and functional changes in specific brain areas.
