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Molecular and neurochemical substrates of the audiogenic seizure strains: The GASH:Sal model
- Source :
- Epilepsy & Behavior. 71:218-225
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- article Purpose:Animalmodelsofaudiogenicepilepsyareusefultoolstounderstandthemechanismsunderlyinghuman reflex epilepsies. There is accumulating evidence regarding behavioral, anatomical, electrophysiological, and genetic substrates of audiogenic seizure strains, but there are still aspects concerning their neurochemical basis that remain to be elucidated. Previous studies have shown the involved of γ-amino butyric acid (GABA) in audiogenic seizures. The aim of our research was to clarify the role of the GABAergic system in the generation of epileptic seizures in the genetic audiogenic seizure-prone hamster (GASH:Sal) strain. Material and methods: We studied the K + /Cl � cotransporter KCC2 and β2-GABAA-type receptor (GABAAR) and β3-GABAAR subunit expressions in the GASH:Sal both at rest and after repeated sound-induced seizures in dif- ferent brain regions using the Western blot technique. We also sequenced the coding region for the KCC2 gene both in wild- type and GASH:Sal hamsters. Results: Lower expressionof KCC2protein wasfoundinGASH:Salwhencomparedwith controls atrest inseveral brain areas: hippocampus, cortex, cerebellum, hypothalamus, pons-medulla, and mesencephalon. Repeated in- duction of seizures caused a decrease in KCC2 protein content in the inferior colliculus and hippocampus and an increase in the pons-medulla. When compared to controls, the basal β2-GABAAR subunit in the GASH:Sal was overexpressed in the inferior colliculus, rest of the mesencephalon, and cerebellum, whereas basal β3 subunit levels were lower in the inferior colliculus and rest of the mesencephalon. Repeated seizures increased β2 both in the inferior colliculus and in the hypothalamus and β3 in the hypothalamus. No differences in the KCC2 gene-coding region were found between GASH:Sal and wild-type hamsters. Conclusions: These data indicate that GABAergic system functioning is impaired in the GASH:Sal strain, and repeated seizures seem to aggravate this dysfunction. These results have potential clinical relevance and support the validity of employing the GASH:Sal strain as a model to study the neurochemistry of genetic reflex epilepsy.
- Subjects :
- 0301 basic medicine
Inferior colliculus
Cerebellum
Hippocampus
Biology
Epilepsy, Reflex
Midbrain
03 medical and health sciences
Behavioral Neuroscience
Epilepsy
0302 clinical medicine
Neurochemical
Seizures
Cricetinae
medicine
Animals
gamma-Aminobutyric Acid
Cerebral Cortex
Mesocricetus
Symporters
Brain
Receptors, GABA-A
medicine.disease
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Acoustic Stimulation
nervous system
Neurology
Hypothalamus
GABAergic
Neurology (clinical)
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15255050
- Volume :
- 71
- Database :
- OpenAIRE
- Journal :
- Epilepsy & Behavior
- Accession number :
- edsair.doi.dedup.....8de8677c52e4270bb1babea3dad3c7e0