Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Institute of Biochemistry, Charité-Universitätsmedizin Berlin, 10117, Berlin, Germany.
Sci Rep. 2021 Apr 21;11(1):8662. doi: 10.1038/s41598-021-87967-5.
The actin binding protein drebrin plays a key role in dendritic spine formation and synaptic plasticity. Decreased drebrin protein levels have been observed in temporal lobe epilepsy, suggesting the involvement of drebrin in the disease. Here we investigated the effect of drebrin knockout on physiological and pathophysiological neuronal network activities in mice by inducing gamma oscillations, involved in higher cognitive functions, and by analyzing pathophysiological epileptiform activity. We found that loss of drebrin increased the emergence of spontaneous gamma oscillations suggesting an increase in neuronal excitability when drebrin is absent. Further analysis showed that although the kainate-induced hippocampal gamma oscillations were unchanged in drebrin deficient mice, seizure like events measured in the entorhinal cortex appeared earlier and more frequently. The results suggest that while drebrin is not essential for normal physiological network activity, it helps to protect against the formation of seizure like activities during pathological conditions. The data indicate that targeting drebrin function could potentially be a preventive or therapeutic strategy for epilepsy treatment.
肌动蛋白结合蛋白 drebrin 在树突棘形成和突触可塑性中发挥关键作用。颞叶癫痫患者中观察到 drebrin 蛋白水平降低，表明 drebrin 参与了该疾病。在这里，我们通过诱导与高级认知功能相关的γ振荡以及分析病理生理癫痫样活动，研究了 drebrin 敲除对小鼠生理和病理生理神经元网络活动的影响。我们发现，当 drebrin 缺失时，drebrin 的缺失增加了自发性γ振荡的出现，表明神经元兴奋性增加。进一步的分析表明，尽管在 drebrin 缺乏的小鼠中，海人酸诱导的海马γ振荡没有改变，但在海马回中测量的类似癫痫发作的事件出现得更早且更频繁。结果表明，尽管 drebrin 对于正常生理网络活动不是必需的，但它有助于防止在病理条件下形成类似癫痫发作的活动。这些数据表明，针对 drebrin 功能可能是治疗癫痫的一种预防或治疗策略。
