Neuroprotective effects of the mood stabilizer lamotrigine against glutamate excitotoxicity: roles of chromatin remodelling and Bcl-2 induction.

The International Journal of Neuropsychopharmacology
Y LengDe-Maw Chuang

Abstract

Lamotrigine (LTG), a phenyltriazine derivative and anti-epileptic drug, has emerged as an effective first-line treatment for bipolar mood disorder. Like the other mood stabilizers lithium and valproate, LTG also has neuroprotective properties but its exact mechanisms remain poorly defined. The present study utilized rat cerebellar granule cells (CGCs) to examine the neuroprotective effects of LTG against glutamate-induced excitotoxicity and to investigate potential underlying mechanisms. CGCs pretreated with LTG were challenged with an excitotoxic dose of glutamate. Pretreatment caused a time- and concentration-dependent inhibition of glutamate excitotoxicity with nearly full protection at higher doses (≥ 100 μm), as revealed by cell viability assays and morphology. LTG treatment increased levels of acetylated histone H3 and H4 as well as dose- and time-dependently enhanced B-cell lymphoma-2 (Bcl-2) mRNA and protein levels; these changes were associated with up-regulation of the histone acetylation and activity of the Bcl-2 promoter. Importantly, lentiviral-mediated Bcl-2 silencing by shRNA reduced both LTG-induced Bcl-2 mRNA up-regulation and neuroprotection against glutamate excitotoxicity. Finally, the co-presence of a sub-e...Continue Reading

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Nov 20, 2013·International Journal of Molecular Sciences·Edward C Lauterbach
Mar 5, 2016·Journal of Psychosocial Nursing and Mental Health Services·Robert H Howland
Jun 10, 2014·Bipolar Disorders·José Luis SantosMiguel Ángel Jiménez-Arriero
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Nov 5, 2021·PloS One·Johan FernströmDaniel Lindqvist

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