title: Intermittent theta-burst stimulation rescues dopamine-dependent corticostriatal synaptic plasticity and motor behavior in experimental parkinsonism: Possible role of glial activity.
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.
  
  
  CONCLUSIONS
  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. © 2017 International Parkinson and Movement Disorder Society.
authors.affiliation: Fondazione Santa Lucia, Istituto di Ricerca e Clinica a Carattere Scientifico (IRCCS), Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Cacace
authors.affiliation: Fondazione Santa Lucia, Istituto di Ricerca e Clinica a Carattere Scientifico (IRCCS), Rome, Italy.
authors.forename: Desirèe
authors.initials: D
authors.lastname: Mineo
authors.affiliation: Fondazione Santa Lucia, Istituto di Ricerca e Clinica a Carattere Scientifico (IRCCS), Rome, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Viscomi
authors.affiliation: Fondazione Santa Lucia, Istituto di Ricerca e Clinica a Carattere Scientifico (IRCCS), Rome, Italy.
authors.forename: Emanuele Claudio
authors.initials: EC
authors.lastname: Latagliata
authors.affiliation: Fondazione Santa Lucia, Istituto di Ricerca e Clinica a Carattere Scientifico (IRCCS), Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Mancini
authors.affiliation: Fondazione Santa Lucia, Istituto di Ricerca e Clinica a Carattere Scientifico (IRCCS), Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Sasso
authors.affiliation: Fondazione Santa Lucia, Istituto di Ricerca e Clinica a Carattere Scientifico (IRCCS), Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Vannelli
authors.affiliation: Fondazione Santa Lucia, Istituto di Ricerca e Clinica a Carattere Scientifico (IRCCS), Rome, Italy.|Università di Roma "La Sapienza," Dipartimento di Psicologia, Centro "Daniel Bovet,", Rome, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Pascucci
authors.affiliation: Fondazione Santa Lucia, Istituto di Ricerca e Clinica a Carattere Scientifico (IRCCS), Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Pendolino
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Marcello
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pelucchi
authors.affiliation: Fondazione Santa Lucia, Istituto di Ricerca e Clinica a Carattere Scientifico (IRCCS), Rome, Italy.|Università di Roma "La Sapienza," Dipartimento di Psicologia, Centro "Daniel Bovet,", Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Puglisi-Allegra
authors.affiliation: Fondazione Santa Lucia, Istituto di Ricerca e Clinica a Carattere Scientifico (IRCCS), Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Molinari
authors.affiliation: Fondazione Santa Lucia, Istituto di Ricerca e Clinica a Carattere Scientifico (IRCCS), Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Picconi
authors.affiliation: Clinica Neurologica, Dipartimento di Medicina, Università degli Studi di Perugia, Ospedale Santa Maria della Misericordia, S. Andrea delle Fratte, Perugia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabresi
authors.affiliation: Fondazione Santa Lucia, Istituto di Ricerca e Clinica a Carattere Scientifico (IRCCS), Rome, Italy.|Dipartimento di Filosofia, Scienze Sociali, Umane e della Formazione, Università degli Studi di Perugia, Perugia, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Ghiglieri
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology; D003342:Corpus Striatum / Q000378:metabolism / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism*; D017781:Genes, Immediate-Early / Q000502:physiology; D008297:Male; D017551:Microdialysis; D017628:Microglia / Q000502:physiology*; D009043:Motor Activity / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D016627:Oxidopamine / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000628:therapy*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D013826:Theta Rhythm / Q000502:physiology; D050781:Transcranial Magnetic Stimulation / Q000379:methods*
chemical_list: D018663:Adrenergic Agents; D016627:Oxidopamine; D004298:Dopamine
keywords: Parkinson's disease; corticostriatal synaptic plasticity; glia; long-term potentiation; transcranial magnetic stimulation