Sialyltransferase ST3Gal IV deletion protects against temporal lobe epilepsy

Abstract

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.

Urinary volatilome analysis in a mouse model of anxiety and depression

“…In contrast, St3gal4-knockout (KO) mice exhibit no epileptic seizures [5]. Furthermore, emotional behavioral tests, including open-field tests, forced swim tests, and fear conditioning tests, showed depression-and anxiety-like symptoms in these mice [5]. We found that kindling stimulation increased growth hormone (GH) levels in neuronal cells and upregulated St3gal4 [14].…”

“…We found that kindling stimulation increased growth hormone (GH) levels in neuronal cells and upregulated St3gal4 [14]. In contrast, St3gal4-KO mice showed downregulation of GH and insulin-like growth factor 1 (Igf1) mRNA in the cerebral cortex [5]. Because GH and IGF1 are the main hormones involved in lipid metabolism, we investigated the relationships between St3gal4 and lipid metabolism using different types of oils to determine the effects of oils on the emotional behaviors of KO mice [15].…”

“…We previously reported that ST3 beta-galactoside alpha-2,3-sialyltransferase IV (St3gal4)deficient mice showed symptoms of anxiety and depression [5]. St3gal4 is one of the six sialyltransferases (St3gal1-6) that generate Sia-2,3Gal linkages on the ends of glycoproteins.…”

“…Genome-wide association studies have demonstrated associations between ST3GAL4 gene variants or single-nucleotide polymorphisms and lipid traits, including high ApoB levels, total cholesterol, triglyceride levels, and coronary artery disease [11,12]. In mouse, St3gal4 expression is region specific, showing abundant expression in the thalamic sensory relay nuclei, including the medial and lateral geniculate, inter geniculate, and ventroposterior nuclei [5,13]. Additionally, St3gal4 is upregulated in neurons located within the neural circuits that exhibit propagation of kindling stimulation [13].…”

“…Additionally, St3gal4 is upregulated in neurons located within the neural circuits that exhibit propagation of kindling stimulation [13]. In contrast, St3gal4-knockout (KO) mice exhibit no epileptic seizures [5]. Furthermore, emotional behavioral tests, including open-field tests, forced swim tests, and fear conditioning tests, showed depression-and anxiety-like symptoms in these mice [5].…”