The onset of abnormal movements in DYT1 dystonia is between childhood and adolescence, although it is unclear why clinical manifestations appear during this developmental period. Plasticity at corticostriatal synapses is critically involved in motor memory. In theTor1a+/ΔgagDYT1 dystonia mouse model, long-term potentiation (LTP) appeared prematurely in a critical developmental window in striatal spiny neurons (SPNs), while long-term depression (LTD) was never recorded. Analysis of dendritic spines showed an increase of both spine width and mature mushroom spines inTor1a+/Δgagneurons, paralleled by an enhanced AMPA receptor (AMPAR) accumulation. BDNF regulates AMPAR expression during development. Accordingly, both proBDNF and BDNF levels were significantly higher inTor1a+/Δgagmice. Consistently, antagonism of BDNF rescued synaptic plasticity deficits and AMPA currents. Our findings demonstrate that early loss of functional and structural synaptic homeostasis represents a unique endophenotypic trait during striatal maturation, promoting the appearance of clinical manifestations in mutation carriers.

Maltese, M., Stanic, J., Tassone, A., Sciamanna, G., Ponterio, G., Vanni, V., et al. (2018). Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum. ELIFE, 7(e33331) [10.7554/eLife.33331].

Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum

Maltese, Marta;Tassone, Annalisa;Sciamanna, Giuseppe;Ponterio, Giulia;Vanni, Valentina;Martella, Giuseppina;Mercuri, Nicola Biagio;Pisani, Antonio
2018-03-05

Abstract

The onset of abnormal movements in DYT1 dystonia is between childhood and adolescence, although it is unclear why clinical manifestations appear during this developmental period. Plasticity at corticostriatal synapses is critically involved in motor memory. In theTor1a+/ΔgagDYT1 dystonia mouse model, long-term potentiation (LTP) appeared prematurely in a critical developmental window in striatal spiny neurons (SPNs), while long-term depression (LTD) was never recorded. Analysis of dendritic spines showed an increase of both spine width and mature mushroom spines inTor1a+/Δgagneurons, paralleled by an enhanced AMPA receptor (AMPAR) accumulation. BDNF regulates AMPAR expression during development. Accordingly, both proBDNF and BDNF levels were significantly higher inTor1a+/Δgagmice. Consistently, antagonism of BDNF rescued synaptic plasticity deficits and AMPA currents. Our findings demonstrate that early loss of functional and structural synaptic homeostasis represents a unique endophenotypic trait during striatal maturation, promoting the appearance of clinical manifestations in mutation carriers.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/26 - Neurologia
English
Con Impact Factor ISI
AMPA receptors; BDNF; dystonia DYT1; mouse; neuroscience; synaptic plasticity
Funding Ministero dell’Istruzione, dell’Università e della Ricerca, PRIN 2010-2011, to Fabrizio Gardoni and Antonio Pisani Dystonia Medical Research Foundation 2017 to Antonio Pisani
Maltese, M., Stanic, J., Tassone, A., Sciamanna, G., Ponterio, G., Vanni, V., et al. (2018). Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum. ELIFE, 7(e33331) [10.7554/eLife.33331].
Maltese, M; Stanic, J; Tassone, A; Sciamanna, G; Ponterio, G; Vanni, V; Martella, G; Imbriani, P; Bonsi, P; Mercuri, Nb; Gardoni, F; Pisani, A
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/195319
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