Laboratory for Synaptic Plasticity, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Physiology, School of Medical Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana.
Laboratory for Synaptic Plasticity, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway; Institute of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.
Neurosci Res. 2023 Jun;191:1-12. doi: 10.1016/j.neures.2022.12.006. Epub 2022 Dec 16.
Expression of immediate early genes (IEGs) in the brain is important for synaptic plasticity, and probably also in neurodegenerative conditions. To understand the cellular mechanisms of the underlying neuropathophysiological processes in epilepsy, we need to pinpoint changes in concentration of synaptic plasticity-related proteins at subsynaptic levels. In this study, we examined changes in synaptic expression of Activity-regulated cytoskeleton-associated (Arc) and Brai Derived Neurotrophic Factor (BDNF) in a rat model of kainate-induced temporal lobe epilepsy (TLE). Western blotting showed reduced concentrations of Arc and increased concentrations of BDNF in hippocampal synaptosomes in chronic TLE rats. Then, using quantitative electron microscopy, we found corresponding changes in subsynaptic regions in the hippocampus. Specifically, we detected significant reductions in the concentrations of Arc in the presynaptic terminal of Schaffer collateral glutamatergic synapses in the stratum radiatum of the CA1 area in TLE, as well as in their adjacent postsynaptic spines. In CA3, there was a significant reduction of Arc only in the presynaptic terminal cytoplasm. Conversely, in CA3, there was a significant increase in the expression of BDNF in the presynaptic terminal, but not in the postsynaptic spine. Significant increase in BDNF concentration in the CA1 postsynaptic density was also obtained. We hypothesize that the observed changes in Arc and BDNF may contribute to both cognitive impairment and increased excitotoxic vulnerability in chronic epilepsy.
脑内即刻早期基因（IEGs）的表达对突触可塑性很重要，可能对神经退行性疾病也很重要。为了了解癫痫症潜在神经病理生理过程中的细胞机制，我们需要确定亚突触水平上与突触可塑性相关的蛋白质浓度变化。在这项研究中，我们检查了在红藻氨酸诱导的颞叶癫痫（TLE）大鼠模型中Arc 和脑源性神经营养因子（BDNF）的突触表达变化。Western blot 显示，慢性 TLE 大鼠海马突触体中的 Arc 浓度降低，BDNF 浓度升高。然后，我们使用定量电子显微镜在海马的亚突触区域发现了相应的变化。具体来说，我们在 TLE 的 CA1 区放射层的 Schaffer 侧枝谷氨酸能突触的突触前末梢中检测到 Arc 浓度的显著降低，以及其相邻的突触后棘突。在 CA3 中，Arc 仅在前突触末梢细胞质中显著减少。相反，在 CA3 中，BDNF 在突触前末梢中的表达显著增加，但在突触后棘突中没有增加。还获得了 CA1 突触后密度中 BDNF 浓度的显著增加。我们假设观察到的 Arc 和 BDNF 的变化可能导致慢性癫痫症中的认知障碍和兴奋性毒性易感性增加。
