Frerker Bernd, Rohde Marco, Müller Steffen, Bien Christian G, Köhling Rüdiger, Kirschstein Timo
Oscar Langendorff Institute of Physiology, University of Rostock, 18057 Rostock, Germany.
Department of Irradiation Therapy, University Hospital of Rostock, 18059 Rostock, Germany.
Brain Sci. 2020 Feb 22;10(2):123. doi: 10.3390/brainsci10020123.
: The conversion of glutamic acid into γ-aminobutyric acid (GABA) is catalyzed by the glutamic acid decarboxylase (GAD). Antibodies against this enzyme have been described in neurological disorders, but the pathophysiological role of these antibodies is still poorly understood. We hypothesized that anti-GAD autoantibodies could diminish the GABA content in the slice and facilitate epileptic activity. : Cerebrospinal fluids (CSF) from two patients containing anti-GAD (A and B) were injected into the rat hippocampus in vivo. Hippocampal slices were prepared for electrophysiological field potential recordings in order to record recurrent epileptic discharges (REDs) in the CA1 region induced by the removal of Mg and/or by adding gabazine. As control groups, we injected an anti-GAD-negative human CSF or saline solution, and we used non-operated naive animals. : RED frequencies were significantly higher in the Mg-free solution than in the gabazine-containing solution. The average frequency of REDs in the last 10 min and the average duration of REDs in the last 5 min did not show significant differences between the anti-GAD-B-treated and the control slices, but in the Mg-free solution, anti-GAD-A had significantly higher epileptic activity than anti-GAD-B. : These results indicate that anti-GAD has distinct effects on the development of spontaneous epileptic activity.
谷氨酸转化为γ-氨基丁酸(GABA)由谷氨酸脱羧酶(GAD)催化。在神经疾病中已发现针对这种酶的抗体,但这些抗体的病理生理作用仍知之甚少。我们推测抗GAD自身抗体可能会降低切片中的GABA含量并促进癫痫活动。
将两名含抗GAD抗体(A和B)患者的脑脊液(CSF)体内注射到大鼠海马体中。制备海马切片用于电生理场电位记录,以记录通过去除镁离子和/或添加荷包牡丹碱诱导的CA1区反复癫痫放电(REDs)。作为对照组,我们注射抗GAD阴性的人脑脊液或生理盐水,并使用未手术的正常动物。
无镁溶液中的RED频率显著高于含荷包牡丹碱的溶液。抗GAD-B处理组切片与对照组切片在最后10分钟的RED平均频率和最后5分钟的RED平均持续时间上没有显著差异,但在无镁溶液中,抗GAD-A的癫痫活性显著高于抗GAD-B。
这些结果表明抗GAD对自发性癫痫活动的发展有明显影响。