Neuroprotective Effects of Doxycycline in the R6/2 Mouse Model of Huntington’s Disease
Autor: | Carmela Giampà, Claudia Balducci, Vincenza D'Angelo, Luisa Artioli, Vladimiro Artuso, Emanuela Paldino, Pietro La Vitola, Gianluigi Forloni, Francesca Fusco |
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Rok vydání: | 2019 |
Předmět: |
Male
0301 basic medicine Excitotoxicity Pharmacology medicine.disease_cause 0302 clinical medicine Cyclic AMP Response Element-Binding Protein Neurons Doxycycline Behavior Animal biology Neurodegeneration Organ Size Huntington Disease Neuroprotective Agents Neurology Female Microglia Disks Large Homolog 4 Protein Huntington’s disease medicine.drug Genetically modified mouse Neuroscience (miscellaneous) Mice Transgenic Motor Activity Settore MED/26 CREB Neuroprotection Article 03 medical and health sciences Cellular and Molecular Neuroscience Huntington's disease Weight Loss medicine Animals Neuroinflammation Inflammation business.industry Brain-Derived Neurotrophic Factor pCREB medicine.disease Survival Analysis Corpus Striatum Disease Models Animal BDNF 030104 developmental biology biology.protein business Open Field Test 030217 neurology & neurosurgery |
Zdroj: | Molecular Neurobiology |
ISSN: | 1559-1182 0893-7648 |
Popis: | 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. Electronic supplementary material The online version of this article (10.1007/s12035-019-01847-8) contains supplementary material, which is available to authorized users. |
Databáze: | OpenAIRE |
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