SGK1.1 limits brain damage after status epilepticus through M current-dependent and independent mechanisms

NEUROBIOLOGY OF DISEASE

卷:153

Article

Martin-Batista, Elva^1,2  Maglio, Laura E.^1,2  Armas-Capote, Natalia^1,2  Hernandez, Guadalberto^1,2  de la Rosa, Diego Alvarez^1,2  Giraldez, Teresa^1,2 

[1] Univ La Laguna, Fac Med, Dept Ciencias Med Basicas, Campus Ciencias Salud Sn, San Cristobal De Laguna 38200, Spain

[2] Inst Tecnol Biomed ITB, Campus Ciencias Salud Sn, San Cristobal De Laguna 38071, Spain

关键词: Serum and glucocorticoid-regulated kinase 1;    KA-induced seizures;    Neuroprotection;    Epilepsy;    Kv7 potassium channels;    Apoptosis;   

DOI  :  10.1016/j.nbd.2021.105317

来源: Elsevier

【 摘 要 】

Epilepsy is a neurological condition associated to significant brain damage produced by status epilepticus (SE) including neurodegeneration, gliosis and ectopic neurogenesis. Reduction of these processes constitutes a useful strategy to improve recovery and ameliorate negative outcomes after an initial insult. SGK1.1, the neuronal isoform of the serum and glucocorticoids-regulated kinase 1 (SGK1), has been shown to increase M-current density in neurons, leading to reduced excitability and protection against seizures. For this study, we used 4?5 months old male transgenic C57BL/6 J and FVB/NJ mice expressing near physiological levels of a constitutively active form of the kinase controlled by its endogenous promoter. Here we show that SGK1.1 activation potently reduces levels of neuronal death (assessed using Fluoro-Jade C staining) and reactive glial activation (reported by GFAP and Iba-1 markers) in limbic regions and cortex, 72 h after SE induced by kainate, even in the context of high seizure activity. This neuroprotective effect is not exclusively through M-current activation but is also directly linked to decreased apoptosis levels assessed by TUNEL assays and quantification of Bim and Bcl-xL by western blot of hippocampal protein extracts. Our results demonstrate that this newly described antiapoptotic role of SGK1.1 activation acts synergistically with the regulation of cellular excitability, resulting in a significant reduction of SE-induced brain damage in areas relevant to epileptogenesis.