EPILEPTOGENESIS | Specific Gene Expression Before and After Seizure in Epileptic EL Mice

Murashima, Yoshiya L.; Suzuki, Jirô; Yoshii, Mitsunobu

doi:10.1016/b978-012373961-2.00132-6

Cited by 3 publications

(2 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings have been substantiated by the histochemical and biochemical analyses of glucose utilization and the study of inhibitory neurotransmission mediated by GABA. The developmental formation of the focus complex epileptogenic zone, which mainly consists of the parietal cortex and the hippocampus, has been hypothesized to be the key to the epileptogenesis in EL mice (Murashima et al., 2009).…”

Section: El Micementioning

confidence: 99%

“…During epileptogenesis, a large number of genes are expressed, and this expression is dependent on the developmental state of the animal as well as the epileptic “state.” Among the genes that are highly expressed are those responsible for free radical production and synaptic reorganization, inducible nitric oxide synthetase, apoptosis regulation ( Bcl‐2, Bcl‐X L , Bax ), neurotrophic factors [brain derived nerve growth factor (BDNF), fibroblast growing factor‐2 ( FGF‐2 ), neurotrophin‐3 ( NT‐3 )], cell cycle reentry [cyclin A, B, D, E , cyclin dependent kinase‐1,‐2,‐4 ( CDK‐1, ‐2, ‐4 )], inflammatory signal transduction [interleukin 1a, ( IL‐1a ), interleukin 1b ( IL‐1b ), tumor necrotizing factor‐a ( TNF‐a ), interleukin 1receptor ( IL‐1r ), interleukin 1 receptor antagonist ( IL‐1ra )], and GABA A receptor–modulating neurosteroids and GABA A receptor subunit reorganization (Murashima et al., 2009).…”

mentioning

confidence: 99%

See 1 more Smart Citation

New therapeutic approaches for epilepsies, focusing on reorganization of the GABA_A receptor subunits by neurosteroids

Murashima

Yoshii

2010

Epilepsia

View full text Add to dashboard Cite

SUMMARYNeurosteroids such as allopregnanolone (THP) act as positive allosteric modulators of c-aminobutyric acid (GABA) A receptors and have exerted anticonvulsant properties. However, their role in the regulation of epileptogenesis is unclear. It has been shown that circulating levels of THP fluctuate during development and seizure episodes. Furthermore, both chronic administration of THP and its withdrawal transiently increase expression of the alpha4 subunit of the GABA A receptor in the brain. The steroidogenic enzymes, 5-alphareductase (5aR) and 3-alpha-hydroxysteroid dehydrogenase (3aHSD) have been identified as well, indicating that various cell types are involved in the biosynthesis of neuroactive steroids in the brain. The purpose of the present study is to examine how GABA A receptor-modulating neurosteroids contribute to the epileptogenesis by using the epileptic mutant EL mouse.Male EL mice and control animals, DDY mice, were used. EL mice show secondary generalized seizures, which initiate primarily at the parietal cortex and generalize through the hippocampus.In the interictal period during development, changes of THP, 5aR, 3aSDH, and GABA A receptor alpha4, gamma2, and delta subunits were investigated by western blotting in the hippocampus.In EL mice, levels of the neurosteroid THP and the steroidogenic enzymes 5aR and 3aSDH significantly increased at 3 weeks of age, and rapidly decreased thereafter (5-10 weeks). The sharp withdrawal was observed before mice experienced frequent seizures. In contrast, GABA A alpha4, gamma2, and delta expressions were upregulated (3-8 weeks).In the brain of EL mice, positive neurosteroids such as THP were withdrawn before mice experienced repetitive seizures, which may likely be a trigger for ictogenesis and epileptogenesis. Furthermore, reorganization of the GABA A receptor subunits may lead to a hypersensitivity of the receptor to neurosteroids. Therefore, GABA A receptor-regulating neurosteroids may be a promising target for the development of novel antiepileptic agents.

show abstract

Section: El Micementioning

confidence: 99%

mentioning

confidence: 99%

New therapeutic approaches for epilepsies, focusing on reorganization of the GABA_A receptor subunits by neurosteroids

Murashima

Yoshii

2010

Epilepsia

View full text Add to dashboard Cite

show abstract

Neuronal mechanism of epileptogenesis in EL mouse

Suzuki¹

2013

Proceedings of the Japan Academy. Ser. B: Physical and Biologic

View full text Add to dashboard Cite

The convulsions of the EL mouse (EL) were described by Imaizumi et al. in 1954 and were established as epilepsy by Suzuki in 1976. The EL mouse has been kept as an inbred strain and is considered one of the best animal models originated in Japan. The mode of inheritance is autosomal dominant, and environmental risk factors for seizure occurrence are hypothesised to contribute to the polygenic background. Paroxysmal activities in the EL brain arise from the parietal cortex (PCX) and are augmented in the hippocampus, demonstrated by electrophysiology and autoradiography using 2-deoxy glucose when clinical symptoms of seizures appeared. The neurons in the EL PCX, where GABA activity is lower than that of DDY PCX demonstrate increased excitability to proprioceptive sensory input. After repetitive seizure-provoking stimuli, seizures are more easily induced, eventually occurring spontaneously. This phenomenon of “abnormal plasticity” is also observed in the EEG, decreasing GABA activity, expression of the immediately early gene, and various biochemical and molecular processes. This phenomenon is similar to the learning or progressive process of certain neurological diseases.

show abstract

Untitled

Murashima¹

2016

JJES

View full text Add to dashboard Cite

EPILEPTOGENESIS | Specific Gene Expression Before and After Seizure in Epileptic EL Mice

Cited by 3 publications

References 12 publications

New therapeutic approaches for epilepsies, focusing on reorganization of the GABA_A receptor subunits by neurosteroids

New therapeutic approaches for epilepsies, focusing on reorganization of the GABA_A receptor subunits by neurosteroids

Neuronal mechanism of epileptogenesis in EL mouse

Untitled

Contact Info

Product

Resources

About

EPILEPTOGENESIS | Specific Gene Expression Before and After Seizure in Epileptic EL Mice

Cited by 3 publications

References 12 publications

New therapeutic approaches for epilepsies, focusing on reorganization of the GABAA receptor subunits by neurosteroids

New therapeutic approaches for epilepsies, focusing on reorganization of the GABAA receptor subunits by neurosteroids

Neuronal mechanism of epileptogenesis in EL mouse

Untitled

Contact Info

Product

Resources

About

New therapeutic approaches for epilepsies, focusing on reorganization of the GABA_A receptor subunits by neurosteroids

New therapeutic approaches for epilepsies, focusing on reorganization of the GABA_A receptor subunits by neurosteroids