Losing Balance Over a Fatty Acid.

Losing Balance Over a Fatty Acid.
Epilepsy Curr. 2019 Mar-Apr;19(2):129-131
Authors: Gross C
Abstract
Deficiency of AMPAR-Palmitoylation Aggravates Seizure Susceptibility Itoh M, Yamashita M, Kaneko M, Okuno H, Abe M, Yamazaki M, Natsume R, Yamada D, Kaizuka T, Suwa R, Sakimura K, Sekiguchi M, Wada K, Hoshino M, Mishina M, Hayashi T. J Neurosci. 2018;38(47):10220-10235. doi:10.1523/JNEUROSCI.1590-18.2018. Epub 2018 Oct 24. PMID: 30355633. Synaptic AMPAR expression controls the strength of excitatory synaptic transmission and plasticity. An excess of synaptic AMPARs leads to epilepsy in response to seizure-inducible stimulation. The appropriate regulation of AMPARs plays a crucial role in the maintenance of the excitatory/inhibitory synaptic balance; however, the detailed mechanisms underlying epilepsy remain unclear. Our previous studies have revealed that a key modification of AMPAR trafficking to and from postsynaptic membranes is the reversible, post-translational S-palmitoylation at the C-termini of receptors. To clarify the role of palmitoylation-dependent regulation of AMPARs in vivo, we generated GluA1 palmitoylation-deficient (Cys811 to Ser substitution) knock-in mice. These mutant male mice showed elevated seizure susceptibility and seizure-induced neuronal activity without impairments in synaptic transmission, gross brain structure, or behavior at the basal level. Disruption of the palmitoylation site was accompanied by upr...

Source: Epilepsy Currents - April 10, 2019 Category: Neurology Tags: Epilepsy Curr Source Type: research