Increase of GQ1b in the hippocampus of mice following kindled-seizures

Temporal lobe epilepsy (TLE) often becomes refractory, and patients with TLE show a high incidence of psychiatric symptoms, including anxiety and depression. Therefore, it is necessary to identify molecules that were previously unknown to contribute to epilepsy and its associated disorders. We previously found that the sialyltransferase ST3Gal IV is upregulated within the neural circuits through which amygdalakindling stimulation propagates epileptic seizures. In contrast, this study demonstrated that kindling stimulation failed to evoke epileptic seizures in ST3Gal IV-deficient mice. Furthermore, approximately 80% of these mice failed to show tonic-clonic seizures with stimulation, whereas all littermate wild-type mice showed tonic-clonic seizures. This indicates that the loss of ST3Gal IV does not cause TLE in mice. Meanwhile, ST3Gal IVdeficient mice exhibited decreased acclimation in the open field test, increased immobility in the forced swim test, enhanced freezing during delay auditory fear conditioning, and sleep disturbances. Thus, the loss of ST3Gal IV modulates anxietyrelated behaviors. These findings indicate that ST3Gal IV is a key molecule in the mechanisms underlying anxiety -a side effect of TLE -and may therefore also be an effective target for treating epilepsy, acting through the same circuits.

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“…) and increased GQ1b levels (Kato et al . ). While seizures were associated with tremendous up‐regulation of ST3Gal IV expression (Okabe et al .…”

Section: Discussionmentioning

confidence: 97%

Sialyltransferase ST3Gal IV deletion protects against temporal lobe epilepsy

Srimontri

Endo

Sakamoto

et al. 2014

Journal of Neurochemistry

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“…Decreased hippocampal levels of the major brain gangliosides were also found in a pilocarpine-induced mouse model of epilepsy (de Freitas et al, 2010). In amygdaloid kindling-mice, a model of temporal lobe epilepsy, increased brain levels of GQ1b increased brain levels of GQ1b compared to wild-type mice were reported, concomitantly with a reduction in the levels of GM1, leading to the speculation that high GQ1b levels could cause seizures in these mice (Kato et al, 2008). Intraventricular infusion of a mix of brain gangliosides (which would contain GQ1b) worsened kindling seizure (Nakamura et al, 1989), while administration of GM1 (Fighera et al, 2006) or GT1b (Yamamoto and Mohanan, 2003) alone protected animals from convulsions induced by injection of glutaric acid or kainic acid into the striatum, respectively.…”

Section: Epilepsymentioning

confidence: 96%

Gangliosides in the Brain: Physiology, Pathophysiology and Therapeutic Applications

et al. 2020

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Gangliosides are glycosphingolipids highly abundant in the nervous system, and carry most of the sialic acid residues in the brain. Gangliosides are enriched in cell membrane microdomains ("lipid rafts") and play important roles in the modulation of membrane proteins and ion channels, in cell signaling and in the communication among cells. The importance of gangliosides in the brain is highlighted by the fact that loss of function mutations in ganglioside biosynthetic enzymes result in severe neurodegenerative disorders, often characterized by very early or childhood onset. In addition, changes in the ganglioside profile (i.e., in the relative abundance of specific gangliosides) were reported in healthy aging and in common neurological conditions, including Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), stroke, multiple sclerosis and epilepsy. At least in HD, PD and in some forms of epilepsy, experimental evidence strongly suggests a potential role of gangliosides in disease pathogenesis and potential treatment. In this review, we will summarize ganglioside functions that are crucial to maintain brain health, we will review changes in ganglioside levels that occur in major neurological conditions and we will discuss their contribution to cellular dysfunctions and disease pathogenesis. Finally, we will review evidence of the beneficial roles exerted by gangliosides, GM1 in particular, in disease models and in clinical trials.

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“…The signal intensity of each ganglioside developed on the HPTLC plate was calculated in individual mice (6 kindled and 6 sham-operated mice) using PDquest software (Biorad,Tokyo, Japan) and analyzed using a combination of Excel and Statview-J 5.0. The analysis demonstrated a decrease of GM1 and increase of GQ1b following kindled seizures (Kato et al, 2008). The increase of GQ1b in the hippocampus following kindled seizures was confirmed by immunofluorescence with anti-GQ1b antibody.…”

Section: Effect Of Ganglioside Expressionsmentioning

confidence: 67%

“…On the other hand, we have focused on clarification of the molecular mechanisms of epilepsy progression using a mesial TLE mouse model, amygdale kindled mice, showing epileptic seizures induced due to the development of abnormal neural plasticity in TLE regions. So far we have found three molecules responsible for epileptogenesis, a growth hormone, a sialyltransferase, and ganglioside GQ1b (Matsuhashi et al, 2003;Kato et al, 2008;Kato et al, 2009). The clarification of signaling mechanisms with these molecules will resolve the pharmacoresistancy and open a path for therapeutic intervention for cases of anxiety and depression in the near future.…”

mentioning

confidence: 99%

Increase of GQ1b in the hippocampus of mice following kindled-seizures

Cited by 10 publications

References 27 publications

Sialyltransferase ST3Gal IV deletion protects against temporal lobe epilepsy

Sialyltransferase ST3Gal IV deletion protects against temporal lobe epilepsy

Gangliosides in the Brain: Physiology, Pathophysiology and Therapeutic Applications

Introduction of a Novel Molecular Mechanism of Epilepsy Progression: Roles of Growth Hormone Signaling in a Mouse Model of Temporal Lobe Epilepsy

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