Transcranial Magnetic Stimulation Exerts “Rejuvenation” Effects on Corticostriatal Synapses after Partial Dopamine Depletion
Background In experimental models of Parkinson's disease (PD), different degrees of degeneration to the nigrostriatal pathway produce distinct profiles of synaptic alterations that depend on progressive changes in N‐methyl‐D‐aspartate receptors (NMDAR)‐mediated functions. Repetitive transcrania...
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| Vydané v: | Movement disorders Ročník 36; číslo 10; s. 2254 - 2263 |
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| Hlavní autori: | , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
| Vydavateľské údaje: |
Hoboken, USA
John Wiley & Sons, Inc
01.10.2021
Wiley Subscription Services, Inc |
| Predmet: | |
| ISSN: | 0885-3185, 1531-8257, 1531-8257 |
| On-line prístup: | Získať plný text |
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| Shrnutí: | Background
In experimental models of Parkinson's disease (PD), different degrees of degeneration to the nigrostriatal pathway produce distinct profiles of synaptic alterations that depend on progressive changes in N‐methyl‐D‐aspartate receptors (NMDAR)‐mediated functions. Repetitive transcranial magnetic stimulation (rTMS) induces modifications in glutamatergic and dopaminergic systems, suggesting that it may have an impact on glutamatergic synapses modulated by dopamine neurotransmission. However, no studies have so far explored the mechanisms of rTMS effects at early stages of PD.
Objectives
We tested the hypothesis that in vivo application of rTMS with intermittent theta‐burst stimulation (iTBS) pattern alleviates corticostriatal dysfunctions by modulating NMDAR‐dependent plasticity in a rat model of early parkinsonism.
Methods
Dorsolateral striatal spiny projection neurons (SPNs) activity was studied through ex vivo whole‐cell patch‐clamp recordings in corticostriatal slices obtained from 6‐hydroxydopamine‐lesioned rats, subjected to a single session (acute) of iTBS and tested for forelimb akinesia with the stepping test. Immunohistochemical analyses were performed to analyze morphological correlates of plasticity in SPNs.
Results
Acute iTBS ameliorated limb akinesia and rescued corticostriatal long‐term potentiation (LTP) in SPNs of partially lesioned rats. This effect was abolished by applying a selective inhibitor of GluN2B‐subunit‐containing NMDAR, suggesting that iTBS treatment could be associated with an enhanced activation of specific NMDAR subunits, which are major regulators of structural plasticity during synapse development. Morphological analyses of SPNs revealed that iTBS treatment reverted dendritic spine loss inducing a prevalence of thin‐elongated spines in the biocytin‐filled SPNs.
Conclusions
Taken together, our data identify that an acute iTBS treatment produces a series of plastic changes underlying striatal compensatory adaptation in the parkinsonian basal ganglia circuit. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society |
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| Bibliografia: | Relevant conflicts of interest/financial disclosures Funding agencies This work was supported by grants from the Fresco Parkinson Institute to New York University School of Medicine and The Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders, which were made possible with support from Marlene and Paolo Fresco (V.G., P.C., and A.C.) and by the Italian Ministry of Health, Ricerca Corrente (B.P. and P.C.). Giuseppina Natale and Annabella Pignataro contributed equally. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
| ISSN: | 0885-3185 1531-8257 1531-8257 |
| DOI: | 10.1002/mds.28671 |