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Title: Reduced fractalkine levels lead to striatal synaptic plasticity deficits in Huntington's disease
Author: Kim, Anya
García, Esther
Straccia, Marco
Comella Bolla, Andrea
Miguez, Andrés
Masana Nadal, Mercè
Alberch i Vié, Jordi
Canals i Coll, Josep M.
Rodríguez Allué, Manuel José
Keywords: Corea de Huntington
Models animals en la investigació
Huntington's chorea
Animal models in research
Issue Date: 18-Jun-2020
Publisher: Frontiers Media
Abstract: Huntington's disease (HD) is an inherited neurodegenerative disorder in which the striatum is the most affected brain region. Although a chronic inflammatory microglial reaction that amplifies disease progression has been described in HD patients, some murine models develop symptoms without inflammatory microglial activation. Thus, dysfunction of non-inflammatory microglial activity could also contribute to the early HD pathological process. Here, we show the involvement of microglia and particularly fractalkine signaling in the striatal synaptic dysfunction of R6/1 mice. We found reduced fractalkine gene expression and protein concentration in R6/1 striata from 8 to 20 weeks of age. Consistently, we also observed a down-regulation of fractalkine levels in the putamen of HD patients and in HD patient hiPSC-derived neurons. Automated cell morphology analysis showed a non-inflammatory ramified microglia in the striatum of R6/1 mice. However, we found increased PSD-95-positive puncta inside microglia, indicative of synaptic pruning, before HD motor symptoms start to manifest. Indeed, microglia appeared to be essential for striatal synaptic function, as the inhibition of microglial activity with minocycline impaired the induction of corticostriatal long-term depression (LTD) in wild-type mice. Notably, fractalkine administration restored impaired corticostriatal LTD in R6/1 mice. Our results unveil a role for fractalkine-dependent neuron-microglia interactions in the early striatal synaptic dysfunction characteristic of HD.
Note: Reproducció del document publicat a:
It is part of: Frontiers in Cellular Neuroscience, 2020, vol. 14, p. 163
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ISSN: 1662-5102
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Biomedicina)

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