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. 2023 Dec;38(12):2173-2184.
doi: 10.1002/mds.29599. Epub 2023 Sep 12.

Astrocyte Responses Influence Local Effects of Whole-Brain Magnetic Stimulation in Parkinsonian Rats

Giuseppina Natale  1 , Micol Colella  2 , Maria De Carluccio  1   3 , Daniele Lelli  2 , Alessandra Paffi  2 , Filippo Carducci  4 , Francesca Apollonio  2 , Daniela Palacios  5   6 , Maria Teresa Viscomi  5   6 , Micaela Liberti  2 , Veronica Ghiglieri  6   7
Affiliations

Astrocyte Responses Influence Local Effects of Whole-Brain Magnetic Stimulation in Parkinsonian Rats

Giuseppina Natale et al. Mov Disord. 2023 Dec.

Abstract

Background: Excessive glutamatergic transmission in the striatum is implicated in Parkinson's disease (PD) progression. Astrocytes maintain glutamate homeostasis, protecting from excitotoxicity through the glutamate-aspartate transporter (GLAST), whose alterations have been reported in PD. Noninvasive brain stimulation using intermittent theta-burst stimulation (iTBS) acts on striatal neurons and glia, inducing neuromodulatory effects and functional recovery in experimental parkinsonism.

Objective: Because PD is associated with altered astrocyte function, we hypothesized that acute iTBS, known to rescue striatal glutamatergic transmission, exerts regional- and cell-specific effects through modulation of glial functions.

Methods: 6-Hydroxydopamine-lesioned rats were exposed to acute iTBS, and the areas predicted to be more responsive by a biophysical, hyper-realistic computational model that faithfully reconstructs the experimental setting were analyzed. The effects of iTBS on glial cells and motor behavior were evaluated by molecular and morphological analyses, and CatWalk and Stepping test, respectively.

Results: As predicted by the model, the hippocampus, cerebellum, and striatum displayed a marked c-FOS activation after iTBS, with the striatum showing specific morphological and molecular changes in the astrocytes, decreased phospho-CREB levels, and recovery of GLAST. Striatal-dependent motor performances were also significantly improved.

Conclusion: These data uncover an unknown iTBS effect on astrocytes, advancing the understanding of the complex mechanisms involved in TMS-mediated functional recovery. Data on numerical dosimetry, obtained with a degree of anatomical details never before considered and validated by the biological findings, provide a framework to predict the electric-field induced in different specific brain areas and associate it with functional and molecular changes. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: GLAST; glia; parkinson's disease; synaptic plasticity; transcranial noninvasive stimulation.

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References

    1. Terao Y, Ugawa Y. Basic mechanisms of TMS. J Clin Neurophysiol 2002;19(4):322-343.
    1. Lefaucheur JP, Aleman A, Baeken C, et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): an update (2014-2018). Clin Neurophysiol 2020;131(2):474-528.
    1. Wagner T, Valero-Cabre A, Pascual-Leone A. Noninvasive human brain stimulation. Annu Rev Biomed Eng 2007;9:527-565.
    1. Cárdenas-Morales L, Volz LJ, Michely J, et al. Network connectivity and individual responses to brain stimulation in the human motor system. Cereb Cortex 2014;24(7):1697-1707.
    1. Valero-Cabré A, Amengual JL, Stengel C, Pascual-Leone A, Coubard OA. Transcranial magnetic stimulation in basic and clinical neuroscience: a comprehensive review of fundamental principles and novel insights. Neurosci Biobehav Rev 2017;83:381-404.