Brain Aminergic Deficiency in Absence Epileptic Rats: Dependency on Seizure Severity and Their Functional Coupling at Rest

• 作者: A. B. Shatskova E. MacDonald G. Van Luijtelaar I. S. Midzyanovskaya L. Tuomisto
• 来源期刊: 行为与脑科学期刊(英文)
• 学科: 医学
• 关键词: ABSENCE Epilepsy Rat Animal Model BRAIN MONOAMINES HISTAMINE
• 年，卷（期）: 2020,（1）
• 页码范围: 29-45
• 页数: 17页
• 分类号: R74

摘要

Brain aminergic tone was examined in rats with different genetically determined generalized epilepsies and in normal rats. Our previously published database was analyzed to examine if there were functional correlations between brain biogenic amines and their metabolic rates within particular cerebral regions. Rats with genetically determined absence (AbS) and/or audiogenic seizures (AGS) served as models for human generalized non-convulsive and convulsive epilepsies. Tissue concentrations of 5-HT, dopamine (DA) and their main metabolites, as well as tryptophan (TRT), histamine (HA) and noradrenaline (NA) were assayed in different brain regions and analyzed for within-regions correlations in non-stressed conditions. It was found that AbS rats had higher indices of DA-ergic metabolism than non-epileptic controls, but the severity of AbS correlated with a widespread dopaminergic deficiency, as expressed in lowered indices of DA metabolism. AGS exerted no major effects on tissue neurochemistry. Brain DA-ergic and 5HT-ergic metabolic indices (measured as the ratio of the metabolite to the parent transmitter) were closely linked in striatum and pons-medulla of AbS rats. Remarkably, the tissue content of HA in pons-medulla of AbS rats displayed correlations with metabolic ratios of 5HT and DA, which was not seen in normal rats. It is hypothesized that enhanced metabolism of DA and 5HT are at least partial compensatory antiepileptic mechanisms in the brain, and a disturbance of this compensation leads to an aggravation of absence seizures.