Bahabry Rudhab, Jago Silvienne Sint, Hauser Rebecca M, Harmon Jonathan, Sheppard Leah Dinah, Oyassan Bellafaith, Lubin Farah D
Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA.
Epilepsy Behav Rep. 2024 Dec 28;29:100735. doi: 10.1016/j.ebr.2024.100735. eCollection 2025 Mar.
The transcriptional mechanisms underlying impaired hippocampal-dependent memory seen in temporal lobe epilepsy (TLE) have been extensively studied in rodent models. While cognitive testing in these models often involves multiple behavioral tasks, the impact of sequential behavioral testing (SBT) on gene transcription changes in epilepsy remains poorly understood. This study utilized the Kainic Acid (KA) TLE rodent model to examine hippocampal gene expression changes influenced by SBT. Our findings indicate reduced anxiety-related behavior, along with impaired spatial and recognition memory and fear memory in epileptic animals. Quantitative PCR (qPCR) analysis revealed an increase in expression in the epilepsy-SBT group compared to control-SBT, while there was a reduction in and . Immunohistochemistry (IHC) showed that in epileptic animals, performing SBT reversed the loss of 5-hydroxymethylcytosine (5-hmC) in the dorsal hippocampus compared to that seen in home-caged (HC) epileptic animals, and this reversal was neuron-driven. These findings highlight the complex interplay between gene transcription and epigenetic regulation during SBT enrichment in the context of epilepsy.
颞叶癫痫（TLE）中所见的海马依赖性记忆受损的转录机制已在啮齿动物模型中得到广泛研究。虽然这些模型中的认知测试通常涉及多个行为任务，但顺序行为测试（SBT）对癫痫中基因转录变化的影响仍知之甚少。本研究利用 kainic 酸（KA）TLE 啮齿动物模型来检查受 SBT 影响的海马基因表达变化。我们的研究结果表明，癫痫动物的焦虑相关行为减少，同时空间记忆、识别记忆和恐惧记忆受损。定量 PCR（qPCR）分析显示，与对照 SBT 组相比，癫痫-SBT 组中 的表达增加，而 和 减少。免疫组织化学（IHC）显示，与笼养（HC）癫痫动物相比，癫痫动物进行 SBT 可逆转背侧海马中 5-羟甲基胞嘧啶（5-hmC）的丢失，且这种逆转是由神经元驱动的。这些发现突出了在癫痫背景下 SBT 富集过程中基因转录和表观遗传调控之间的复杂相互作用。
