Alterations of Calcium Channels in a Mouse Model of Huntington's Disease and Neuroprotection by Blockage of CaV1 Channels. (June 2019)

• Record Type: Journal Article
• Authors: Miranda, Artur S.; Cardozo, Pablo Leal; Silva, Flavia R.; de Souza, Jessica M.; Olmo, Isabella G.; Cruz, Jader S.; Gomez, Marcus Vinícius; Ribeiro, Fabiola M.; Vieira, Luciene B.
• Is Part Of: ASN neuro. Volume 11(2019)
• Publication Date: 2019-06
• Subjects: BACHD mice -- calcium channel blockers -- Cav1 channels -- Huntington's disease -- neurodegeneration -- neuroprotection; Neurosciences -- Periodicals; Molecular neurobiology -- Periodicals; 573.8
• DOI: 10.1177/1759091419856811
• Languages: English
• ISSNs: 1759-0914

Abstract

Huntington's disease (HD) is a neurodegenerative autosomal dominant disorder, characterized by symptoms of involuntary movement of the body, loss of cognitive function, psychiatric disorder, leading inevitably to death. It has been previously described that higher levels of brain expression of Cav 1 channels are involved in major neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. Our results demonstrate that a bacterial artificial chromosome (BAC)-mediated transgenic mouse model (BACHD mice) at the age of 3 and 12 months exhibits significantly increased Cav 1.2 protein levels in the cortex, as compared with wild-type littermates. Importantly, electrophysiological analyses confirm a significant increase in L-type Ca 2+ currents and total Ca 2+ current density in cortical neurons from BACHD mice. By using an in vitro assay to measure neuronal cell death, we were able to observe neuronal protection against glutamate toxicity after treatment with Cav 1 blockers, in wild-type and, more importantly, in BACHD neurons. According to our data, Cav 1 blockers may offer an interesting strategy for the treatment of HD. Altogether, our results show that mutant huntingtin (mHtt) expression may cause a dysregulation of Cav 1.2 channels and we hypothesize that this contributes to neurodegeneration during HD.