Hoeller Alexandre Ademar, de Carvalho Cristiane Ribeiro, Franco Pedro Leite Costa, Formolo Douglas Affonso, Imthon Alexandre Kracker, Dos Santos Henrique Rodighero, Eidt Ingrid, Souza Gabriel Roman, Constantino Leandra Celso, Ferreira Camila Leite, Prediger Rui Daniel, Bainy Leal Rodrigo, Walz Roger
Graduate Program in Medical Science, Center of Health Sciences, University Hospital, Federal University of Santa Catarina, Florianópolis 88040-970, SC, Brazil.
Center of Applied Neuroscience (CeNAp), University Hospital, Federal University of Santa Catarina, Florianópolis 88040-970, SC, Brazil.
Pharmaceuticals (Basel). 2017 Sep 13;10(3):75. doi: 10.3390/ph10030075.
(1) Objectives: Epilepsy disorder is likely to increase with aging, leading to an increased incidence of comorbidities and mortality. In spite of that, there is a lack of information regarding this issue and little knowledge of cognitive and emotional responses in aging subjects following epileptogenesis. We investigated whether and how aging distress epilepsy-related behavioral and biochemical outcomes are associated with cognition and emotion. (2) Methods: Young and middle-aged Wistar rats (3 or 12 months old) were treated with pentylenetetrazol (PTZ, 35 mg/kg) and injected on alternated days for 20 (young rats) and 32 days (middle-aged rats). Kindling was reached after two consecutive stages 4 plus one stage 5 or 6 in Racine scale. Control and kindled rats were evaluated in the elevated plus-maze (EPM) and object-recognition tests and their hippocampus was collected 24 h later for mitogen-activated protein kinases (MAPK) dosage. (3) Results: Middle-aged rats presented a higher resistance to develop kindling, with a decrease in the seizure severity index observed following the 4th and 9th PTZ injections. Middle-aged rats displayed an increased duration of the first myoclonic seizure and an increased latency to the first generalized seizure when compared to younger rats. The induction of kindling did not impair the animals' performance (regardless of age) in the object-recognition task and the EPM test as well as it did not alter the hippocampal levels of MAPKs. (4) Significance: Our findings reveal that, despite age-related differences during epileptogenesis, middle-aged rats evaluated after kindling performed similarly during discriminative learning and emotional tasks in comparison to young animals, with no alteration of hippocampal MAPKs. Additional investigation must be carried out to explore the electrophysiological mechanisms underlying these responses, as well as the long-term effects displayed after kindling.
(1) 目的：癫痫障碍可能随年龄增长而增加，导致合并症发病率和死亡率上升。尽管如此，关于这一问题的信息匮乏，对癫痫发生后老年受试者的认知和情绪反应了解甚少。我们研究了衰老应激与癫痫相关的行为和生化结果是否以及如何与认知和情绪相关联。(2) 方法：将年轻和中年Wistar大鼠（3或12月龄）用戊四氮（PTZ，35mg/kg）处理，隔天注射，年轻大鼠注射20天，中年大鼠注射32天。在Racine量表中连续两个4期加一个5期或6期后达到点燃。对对照和点燃大鼠进行高架十字迷宫（EPM）和物体识别测试，并在24小时后收集其海马体用于丝裂原活化蛋白激酶（MAPK）定量分析。(3) 结果：中年大鼠对点燃的抵抗力更高，在第4次和第9次PTZ注射后观察到癫痫发作严重程度指数降低。与年轻大鼠相比，中年大鼠首次肌阵挛性发作的持续时间增加，首次全身性发作的潜伏期延长。点燃的诱导并未损害动物在物体识别任务和EPM测试中的表现（无论年龄），也未改变海马体中MAPK的水平。(4) 意义：我们的研究结果表明，尽管在癫痫发生过程中存在与年龄相关的差异，但点燃后评估的中年大鼠在辨别学习和情绪任务中的表现与年轻动物相似，海马体MAPK未发生改变。必须进行进一步的研究以探索这些反应背后的电生理机制，以及点燃后显示的长期影响。
