Ganglioside GM3 synthase (α-2,3-sialyltransferase, ST3GAL5, GM3S) is a key enzyme involved in the biosynthesis of gangliosides. ST3GAL5 deficiency causes an absence of GM3 and all downstream biosynthetic derivatives. The affected individuals manifest deafness, severe irritability, intractable seizures, and profound intellectual disability. To investigate whether deficiency of GM3 is involved in seizure susceptibility, we induced seizures with different chemoconvulsants in ST3GAL5 knockout mice. We report here that ST3GAL5 knockout mice are hyperactive and more susceptible to seizures induced by chemoconvulsants, including kainate and pilocarpine, compared with normal controls. In the hippocampal dentate gyrus, loss of GM3 aggravates seizure-induced aberrant neurogenesis. These data indicate that GM3 and gangliosides derived from GM3 may serve as important regulators of epilepsy and may play an important role in aberrant neurogenesis associated with seizures.

神经节苷脂 GM3 合酶（α-2,3-唾液酸转移酶，ST3GAL5，GM3S）是参与神经节苷脂生物合成的关键酶。ST3GAL5 缺乏导致 GM3 和所有下游生物合成衍生物的缺失。受影响的个体表现出耳聋、严重易怒、顽固性癫痫发作和严重的智力障碍。为了研究 GM3 的缺乏是否与癫痫易感性有关，我们在 ST3GAL5 基因敲除小鼠中用不同的化学惊厥药诱导癫痫发作。我们在此报告，与正常对照相比，ST3GAL5 基因敲除小鼠活动过度，更容易受到化学惊厥药（包括红藻氨酸和毛果芸香碱）诱导的癫痫发作。在海马齿状回中，GM3 的缺失加剧了癫痫引起的异常神经发生。