Increased Seizure Susceptibility in a Mouse with Diacylglycerol Kinase &amp;lt;i&amp;gt;β&amp;lt;/i&amp;gt; Deficiency

Mitsue Ishisaka,Naoaki Saito,Kazuhiro Tsuruma,Masamitsu Shimazawa,Yasuhito Shirai,Hideaki Hara

doi:10.4236/nm.2013.42019

Increased Seizure Susceptibility in a Mouse with Diacylglycerol Kinase &lt;i&gt;β&lt;/i&gt; Deficiency

Mitsue Ishisaka, Naoaki Saito + Show 4 more

Open Access

https://doi.org/10.4236/nm.2013.42019

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Abstract

Diacylglycerol kinase (DGK) is an enzyme that converts diacylglycerol to phosphatidic acid. Several DGK isoforms have been implicated in the pathogenesis of seizure, but the role of DGKβ in seizure is unknown. In the present study, we investigated the involvement of DGKβ in seizure using DGKβ knockout (KO) mice. Seizures were more severe in DGKβ KO mice than in wild-type (WT) mice after pentylenetetrazol (PTZ) treatment and after kainic acid treatment, but there were no differences in latency to seizure. The expression levels of DGKβ in the hippocampal CA1, CA3, or DG areas did not differ between PTZ (60 mg/kg) treatment and saline treatment. There were fewer parvalbumin-positive interneurons in the hippocampal CA3 area in DGKβ KO mice than in control WT mice, which might partly account for the increased seizure susceptibility displayed by DGKβ KO mice. These results suggest that DGKβ may play a pivotal role in the development of the relevant interneurons, and that on inherent deficiency of DGKβ increases the animal’s sensitivity to seizure-inducing stimuli.

Highlights

The term “epilepsy” covers a common and diverse set of chronic neurological disorders, and in many cases, it is characterized by seizures
The number of seizures scored 2 or 4 was greater for Diacylglycerol Kinase β (DGKβ) KO mice than for WT mice (Figure 1(d)). These results suggest that DGKβ KO mice have an elevated sensitivity to PTZ
DGKβ is localized in neurons and its expression has been detected in the olfactory bulb, hippocampus, cortex, and striatum [6,7]

Summary

Introduction

The term “epilepsy” covers a common and diverse set of chronic neurological disorders, and in many cases, it is characterized by seizures. It can be caused by an abnormality of brain tissues, such as a brain tumor or head injury, or by disruption of the balance between inhibitory and excitatory neurons in the brain. It has been reported that the excitability of principal hippocampal neurons increases with age, and that more than a third of epileptic patients are over 65 years of age [2]. To judge from these reports, the inhibitory-excitatory balance among neurons may be important in epilepsy. Genetic factors play an important role, and various mutations (for example, in ion channels) have been reported in epileptic individuals [3]

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Conclusion