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

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

  • Neurobiol Dis. 2021 Jun;153:105317. doi: 10.1016/j.nbd.2021.105317.
Elva Martin-Batista 1,  Laura E Maglio 2,  Natalia Armas-Capote 3,  Guadalberto Hernández 4,  Diego Alvarez de la Rosa 5,  Teresa Giraldez 6
Affiliations

Affiliations

  • 1 Departamento de Ciencias Médicas Básicas, Facultad de Medicina, Universidad de La Laguna, Campus de Ciencias de la Salud sn, 38200 San Cristobal de La Laguna, Spain; Instituto de Tecnologías Biomédicas (ITB), Campus de Ciencias de la Salud sn, 38071 San Cristobal de La Laguna, Spain. Electronic address: [email protected].
  • 2 Departamento de Ciencias Médicas Básicas, Facultad de Medicina, Universidad de La Laguna, Campus de Ciencias de la Salud sn, 38200 San Cristobal de La Laguna, Spain; Instituto de Tecnologías Biomédicas (ITB), Campus de Ciencias de la Salud sn, 38071 San Cristobal de La Laguna, Spain. Electronic address: [email protected].
  • 3 Departamento de Ciencias Médicas Básicas, Facultad de Medicina, Universidad de La Laguna, Campus de Ciencias de la Salud sn, 38200 San Cristobal de La Laguna, Spain; Instituto de Tecnologías Biomédicas (ITB), Campus de Ciencias de la Salud sn, 38071 San Cristobal de La Laguna, Spain. Electronic address: [email protected].
  • 4 Departamento de Ciencias Médicas Básicas, Facultad de Medicina, Universidad de La Laguna, Campus de Ciencias de la Salud sn, 38200 San Cristobal de La Laguna, Spain; Instituto de Tecnologías Biomédicas (ITB), Campus de Ciencias de la Salud sn, 38071 San Cristobal de La Laguna, Spain. Electronic address: [email protected].
  • 5 Departamento de Ciencias Médicas Básicas, Facultad de Medicina, Universidad de La Laguna, Campus de Ciencias de la Salud sn, 38200 San Cristobal de La Laguna, Spain; Instituto de Tecnologías Biomédicas (ITB), Campus de Ciencias de la Salud sn, 38071 San Cristobal de La Laguna, Spain. Electronic address: [email protected].
  • 6 Departamento de Ciencias Médicas Básicas, Facultad de Medicina, Universidad de La Laguna, Campus de Ciencias de la Salud sn, 38200 San Cristobal de La Laguna, Spain; Instituto de Tecnologías Biomédicas (ITB), Campus de Ciencias de la Salud sn, 38071 San Cristobal de La Laguna, Spain. Electronic address: [email protected].
PMID: 33639207 DOI: 10.1016/j.nbd.2021.105317
Abstract

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.

Keywords

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

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