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 the Tor1a+/∆ gagDYT1 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 in Tor1a+/∆gagneurons, paralleled by an enhanced AMPA receptor (AMPAR) accumulation. BDNF regulates AMPAR expression during development. Accordingly, both proBDNF and BDNF levels were significantly higher in Tor1a+/∆gagmice. 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.

Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum / M. Maltese, J. Stanic, A. Tassone, G. Sciamanna, G. Ponterio, V. Vanni, G. Martella, P. Imbriani, P. Bonsi, N.B. Mercuri, F. Gardoni, A. Pisani. - In: ELIFE. - ISSN 2050-084X. - 7:(2018), pp. e33331.1-e33331.23. [10.7554/eLife.33331]

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

J. Stanic;F. Gardoni;
2018

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 the Tor1a+/∆ gagDYT1 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 in Tor1a+/∆gagneurons, paralleled by an enhanced AMPA receptor (AMPAR) accumulation. BDNF regulates AMPAR expression during development. Accordingly, both proBDNF and BDNF levels were significantly higher in Tor1a+/∆gagmice. 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.
AMPA receptors; BDNF; dystonia DYT1; mouse; neuroscience; synaptic plasticity; Neuroscience (all); Biochemistry, Genetics and Molecular Biology (all); Immunology and Microbiology (all)
Settore BIO/14 - Farmacologia
   Discinesia indotta dalla L-DOPA nella malattia di Parkinson: nuovi meccanismi e targets molecolari.
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
   2010AHHP5H_002
2018
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/582929
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