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2020-06-18

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cc-by (c) Kim, Anya et al., 2020
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/171294

Reduced fractalkine levels lead to striatal synaptic plasticity deficits in Huntington's disease

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Recurs relacionat

https://doi.org/10.3389/fncel.2020.00163

Resum

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.

Matèries

Corea de Huntington, Models animals en la investigació, Citoquines

Matèries (anglès)

Huntington's chorea, Animal models in research, Cytokines

Citació

Col·leccions

Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

KIM, Anya, et al. Reduced fractalkine levels lead to striatal synaptic plasticity deficits in Huntington's disease. Frontiers in Cellular Neuroscience. 2020. Vol. 14, num. 163. ISSN 1662-5102. [consulted: 6 of August of 2026]. Available at: https://hdl.handle.net/2445/171294

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