Aerobic exercise alters DNA hydroxymethylation levels in an experimental rodent model of temporal lobe epilepsy

IF 1.8 Q3 CLINICAL NEUROLOGY

Epilepsy and Behavior Reports Pub Date : 2024-01-01 DOI:10.1016/j.ebr.2023.100642

Silvienne C. Sint Jago , Rudhab Bahabry , Anna Maria Schreiber , Julia Homola , Tram Ngyuen , Fernando Meijia , Jane B. Allendorfer , Farah D. Lubin

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Abstract

The therapeutic potential of aerobic exercise in mitigating seizures and cognitive issues in temporal lobe epilepsy (TLE) is recognized, yet the underlying mechanisms are not well understood. Using a rodent TLE model induced by Kainic acid (KA), we investigated the impact of a single bout of exercise (i.e., acute) or 4 weeks of aerobic exercise (i.e., chronic). Blood was processed for epilepsy-associated serum markers, and DNA methylation (DNAme), and hippocampal area CA3 was assessed for gene expression levels for DNAme-associated enzymes. While acute aerobic exercise did not alter serum Brain-Derived Neurotrophic Factor (BDNF) or Interleukin-6 (IL-6), chronic exercise resulted in an exercise-specific decrease in serum BDNF and an increase in serum IL-6 levels in epileptic rats. Additionally, whole blood DNAme levels, specifically 5-hydroxymethylcytosine (5-hmC), decreased in epileptic animals following chronic exercise. Hippocampal CA3 5-hmC levels and ten-eleven translocation protein (TET1) expression mirrored these changes. Furthermore, immunohistochemistry analysis revealed that most 5-hmC changes in response to chronic exercise were neuron-specific within area CA3 of the hippocampus. Together, these findings suggest that DNAme mechanisms in the rodent model of TLE are responsive to chronic aerobic exercise, with emphasis on neuronal 5-hmC DNAme in the epileptic hippocampus.

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有氧运动可改变颞叶癫痫实验啮齿动物模型中的 DNA 羟甲基化水平

有氧运动在缓解颞叶癫痫（TLE）发作和认知问题方面的治疗潜力已得到认可，但其潜在机制还不十分清楚。我们使用凯尼酸（KA）诱导的啮齿类 TLE 模型，研究了单次运动（即急性）或 4 周有氧运动（即慢性）的影响。我们对血液进行了处理，以检测与癫痫相关的血清标记物和DNA甲基化（DNAme），并对海马CA3区DNAme相关酶的基因表达水平进行了评估。虽然急性有氧运动不会改变癫痫大鼠的血清脑源性神经营养因子（BDNF）或白细胞介素-6（IL-6），但慢性运动会导致癫痫大鼠血清BDNF的运动特异性降低和血清IL-6水平的升高。此外，癫痫动物的全血DNAme水平，特别是5-羟甲基胞嘧啶（5-hmC）水平，在慢性运动后有所下降。海马CA3 5-hmC水平和十-十一转位蛋白（TET1）的表达也反映了这些变化。此外，免疫组化分析表明，慢性运动引起的大多数 5-hmC 变化是海马 CA3 区神经元特异性的。这些研究结果表明，啮齿动物TLE模型中的DNAme机制对慢性有氧运动有反应，重点是癫痫海马中神经元的5-hmC DNAme。

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