Wnt Signaling Modulators Exhibit Neuroprotective Effects via Combating Astrogliosis and Balancing Synaptic Density at Early and Late Stage Temporal Lobe Epilepsy

IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Kajal Rawat, Vipasha Gautam, Arushi Sandhu, Anil Kumar, Antika Sharma, Alka Bhatia, Lekha Saha
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Abstract

Temporal Lobe Epilepsy (TLE) is a severe neurological condition characterized by recurrent seizures that often do not respond well to available anti-seizure medications. TLE has been associated with epileptogenesis, a process that starts during the latent period following a neurologic insult and is followed by chronic phase. Recent research has linked canonical Wnt signaling to the pathophysiology of epileptogenesis and TLE. Our previous study demonstrated differential regulation of canonical Wnt signaling during early and late stage post status epilepticus (SE) induction. Building on these findings, our current study utilized Wnt modulators: GSK-3β inhibitor 6-bromoindirubin-3’-oxime (6-Bio) and disheveled inhibitor niclosamide and investigated their impact on canonical Wnt signaling during the early (30 days) and later stages (60 days) following SE induction. We assessed several parameters, including seizure frequency, astrogliosis, synaptic density, and neuronal counts in hippocampal tissue. We used immunohistochemistry and Nissl staining to evaluate gliosis, synaptic density, and neuronal counts in micro-dissected hippocampi. Western blotting was used to examine the expression of proteins involved in canonical Wnt/β-catenin signaling, and real-time PCR was conducted to analyze their relative mRNA expression. Wnt modulators, 6-Bio and Niclosamide were found to reduce seizure frequency and various other parameters including behavioral parameters, hippocampal morphology, astrogliosis and synaptic density at different stages of TLE.

Graphical Abstract

Abstract Image

Wnt信号调节剂通过抑制星形胶质细胞增生和平衡颞叶癫痫早期和晚期的突触密度发挥神经保护作用
颞叶癫痫(TLE)是一种严重的神经系统疾病,其特点是反复发作,对现有的抗癫痫药物往往反应不佳。颞叶癫痫与癫痫发生有关,癫痫发生过程始于神经系统损伤后的潜伏期,随后进入慢性期。最近的研究将典型 Wnt 信号与癫痫发生和 TLE 的病理生理学联系起来。我们之前的研究表明,在癫痫状态(SE)诱发后的早期和晚期阶段,典型 Wnt 信号的调控存在差异。基于这些发现,我们目前的研究利用了 Wnt 调节剂:GSK-3β抑制剂6-溴靛红-3'-肟(6-Bio)和disheveled抑制剂烟酰胺,研究了它们对SE诱导后早期(30天)和晚期(60天)典型Wnt信号的影响。我们评估了几个参数,包括癫痫发作频率、星形胶质细胞增多、突触密度和海马组织中的神经元数量。我们使用免疫组化和Nissl染色来评估显微解剖海马的胶质细胞增生、突触密度和神经元数量。Western印迹法检测了参与典型Wnt/β-catenin信号转导的蛋白质的表达,实时PCR分析了它们的相对mRNA表达。研究发现,Wnt调节剂、6-Bio和Niclosamide能降低TLE不同阶段的发作频率和其他各种参数,包括行为参数、海马形态、星形胶质细胞增生和突触密度。
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来源期刊
Neurochemical Research
Neurochemical Research 医学-神经科学
CiteScore
7.70
自引率
2.30%
发文量
320
审稿时长
6 months
期刊介绍: Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.
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