Change of intracellular calcium level causes acute neurotoxicity by antisense oligonucleotides via CSF route.

ABSTRACT: Antisense oligonucleotides (ASOs) are promising therapeutics for intractable central nervous system (CNS) diseases. For this clinical application, neurotoxicity is one of the critical limitations. Therefore, an evaluation of this neurotoxicity from a behavioral perspective is important to reveal symptomatic dysfunction of the CNS and elucidate the underlying molecular mechanism. We here exploited a behavioral analysis method to categorize and quantify the acute neurotoxicity of mice administered with toxic ASOs via intracerebroventricular injection. The toxic ASOs were found to reduce consciousness and locomotor function in mice in a dose-dependent manner. Mechanistically, we analyzed the effects of modulators against receptors or channels, which regulate calcium influx of neurons, on the

SUBMITTER: Jia C 

PROVIDER: S-EPMC9843489 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature