Intermittent theta-burst stimulation rescues dopamine-dependent corticostriatal synaptic plasticity and motor behavior in experimental parkinsonism: Possible role of glial activity

Fabrizio Cacace, Desirèe Mineo, Maria Teresa Viscomi, Emanuele Claudio Latagliata, Maria Mancini, Valeria Sasso, Anna Vannelli, Tiziana Pascucci, Valentina Pendolino, Elena Marcello, Silvia Pelucchi, Stefano Puglisi-Allegra, Marco Molinari, Barbara Picconi, Paolo Calabresi, Veronica Ghiglieri

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Recent studies support the therapeutic utility of repetitive transcranial magnetic stimulation in Parkinson's disease (PD), whose progression is correlated with loss of corticostriatal long-term potentiation and long-term depression. Glial cell activation is also a feature of PD that is gaining increasing attention in the field because astrocytes play a role in chronic neuroinflammatory responses but are also able to manage dopamine (DA) levels. Methods: Intermittent theta-burst stimulation protocol was applied to study the effect of therapeutic neuromodulation on striatal DA levels measured by means of in vivo microdialysis in 6-hydroxydopamine-hemilesioned rats. Effects on corticostriatal synaptic plasticity were studied through in vitro intracellular and whole-cell patch clamp recordings while stepping test and CatWalk were used to test motor behavior. Immunohistochemical analyses were performed to analyze morphological changes in neurons and glial cells. Results: Acute theta-burst stimulation induced an increase in striatal DA levels in hemiparkinsonian rats, 80 minutes post-treatment, correlated with full recovery of plasticity and amelioration of motor performances. With the same timing, immediate early gene activation was restricted to striatal spiny neurons. Intense astrocytic and microglial responses were also significantly reduced 80 minutes following theta-burst stimulation. Conclusion: Taken together, these results provide a first glimpse on physiological adaptations that occur in the parkinsonian striatum following intermittent theta-burst stimulation and may help to disclose the real potential of this technique in treating PD and preventing DA replacement therapy-associated disturbances.

Original languageEnglish
Pages (from-to)1035-1046
Number of pages12
JournalMovement Disorders
Volume32
Issue number7
DOIs
Publication statusPublished - Jul 1 2017

Keywords

  • corticostriatal synaptic plasticity
  • glia
  • long-term potentiation
  • Parkinson's disease
  • transcranial magnetic stimulation

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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