Neuroprotective Effects of Doxycycline in the R6/2 Mouse Model of Huntington's Disease

Emanuela Paldino, Claudia Balducci, Pietro La Vitola, Luisa Artioli, Vincenza D'Angelo, Carmela Giampà, Vladimiro Artuso, Gianluigi Forloni, Francesca R Fusco

Research output: Contribution to journalArticle

Abstract

Mechanisms of tissue damage in Huntington's disease involve excitotoxicity, mitochondrial damage, and inflammation, including microglia activation. Immunomodulatory and anti-protein aggregation properties of tetracyclines were demonstrated in several disease models. In the present study, the neuroprotective and anti-inflammatory effects of the tetracycline doxycycline were investigated in the mouse model of HD disease R6/2. Transgenic mice were daily treated with doxycycline 20 mg/kg, starting from 4 weeks of age. After sacrifice, histological and immunohistochemical studies were performed. We found that doxycycline-treated R6/2 mice survived longer and displayed less severe signs of neurological dysfunction than the saline-treated ones. Primary outcome measures such as striatal atrophy, neuronal intranuclear inclusions, and the negative modulation of microglial reaction revealed a neuroprotective effect of the compound. Doxycycline provided a significantly increase of activated CREB and BDNF in the striatal neurons, along with a down modulation of neuroinflammation, which, combined, might explain the beneficial effects observed in this model. Our findings show that doxycycline treatment could be considered as a valid therapeutic approach for HD.

Original languageEnglish
JournalMolecular Neurobiology
DOIs
Publication statusE-pub ahead of print - Dec 26 2019

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