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
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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