Ethosuximide

Ethosuximide(ETH) enhances hippocampal derived NSC proliferation and neurospheres formation in vitro. Low concentration of ETH induces proliferation of NSC, while higher concentrations of ETH are cytotoxic. Also, ETH activates the PI3K/Akt signal transduction pathway in adult hippocampal NSC in vitro. Blockade of the PI3K/Akt pathway inhibits ETH induced hippocampal NSC neuronal differentiation^[3].

Mouse Neuro2A (N2A) neuroblastoma cells are cultured on 6-well plates and treated with retinoic acid to induce neuronal differentiation. After 24 h, N2A cells are treated with vehicle control (PBS) or increasing concentrations of ethosuximide for 5 h. Total RNA is then isolated, DNase-treated and reverse transcribed to cDNA. qRT-PCR is run above normalising to the reference genes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and β-actin (ACTB).

Anti-epileptic drug ethosuximide rescues the short lifespan and chemosensory defects exhibited by C. elegans null mutants of dnj-14, the worm orthologue of the DNAJC5 gene mutated in autosomal-dominant adult-onset neuronal ceroid lipofuscinosis. It also ameliorates the locomotion impairment and short lifespan of worms expressing a human Tau mutant that causes frontotemporal dementia^[1]. Ethosuximide extends lifespan by inhibiting the function of specific chemosensory neurons^[2]. It increases neurogenesis, reduces neurodegeneration, and reverses cognitive impairments in rat model of AD like phenotypes^[3].