Pyroptotic cell death in the R6/2 mouse model of Huntington's disease: new insight on the inflammasome

Emanuela Paldino; Vincenza D'Angelo; Giuseppe Sancesario; Francesca R Fusco

doi:10.1038/s41420-020-00293-z

Pyroptotic cell death in the R6/2 mouse model of Huntington's disease: new insight on the inflammasome

Cell Death Discov. 2020 Jul 31:6:69. doi: 10.1038/s41420-020-00293-z. eCollection 2020.

Authors

Emanuela Paldino¹, Vincenza D'Angelo², Giuseppe Sancesario², Francesca R Fusco¹

Affiliations

¹ IRCSS Fondazione Santa Lucia, Laboratory of Neuroanatomy, Via del Fosso di Fiorano, 64, 00143 Rome, Italy.
² Department of Systems Medicine, Tor Vergata University of Rome, via Montpellier 1, 00133 Rome, Italy.

Abstract

Mechanisms of tissue damage in Huntington's disease involve excitotoxicity, mitochondrial damage, and neuroinflammation, including microglia activation. In the present study, we investigate the role of pyroptosis process in the striatal neurons of the R6/2 mouse model of Huntington's disease. Transgenic mice were sacrificed at 4 and 13 weeks of age. After sacrifice, histological and immunohistochemical studies were performed. We found that NLRP3 and Caspase-1 were intensely expressed in 13-week-old R6/2 mice. Moreover, NLRP3 expression levels were higher in striatal spiny projection neurons and in parvalbumin interneurons, which are prone to degenerate in HD.

Keywords: Cellular neuroscience; Huntington's disease.