Réus Gislaine Z, Scaini Giselli, Jeremias Gabriela C, Furlanetto Camila B, Morais Meline O S, Mello-Santos Lis Maira, Quevedo João, Streck Emilio L
Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Laboratório de Bioenergética, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil.
Brain Res. 2014 Oct 2;1583:269-76. doi: 10.1016/j.brainres.2014.08.010. Epub 2014 Aug 13.
Methylphenidate (MPH) is commonly prescribed for children who have been diagnosed with attention deficit hyperactivity disorder (ADHD); however, the action mechanisms of methylphenidate have not been fully elucidated. Studies have shown a relationship between apoptosis signaling pathways and psychiatric disorders, as well as in therapeutic targets for such disorders. So, we investigated if chronic treatment with MPH at doses of 1, 2 and 10mg/kg could alter the levels of pro-apoptotic protein, Bax, anti-apoptotic protein, Bcl-2, caspase-3 and cytochrome c in the brain of young and adult Wistar rats. Our results showed that MPH at all doses increased Bax in the cortex; the Bcl-2 and caspase-3 were increased with MPH (1mg/kg) and were reduced with MPH (2 and 10mg/kg); the cytochrome c was reduced in the cortex after treatment with MPH at all doses; in the cerebellum there was an increase of Bax with MPH at all doses, however, there was a reduction of Bcl-2, caspase-3, and cytochrome c with MPH (2 and 10mg/kg); in the striatum the treatment with MPH (10mg/kg) decreased caspase-3 and cytochrome c; treatment with MPH (2 and 10mg/kg) increased Bax and decreased Bcl-2 in the hippocampus; and the caspase-3 and cytochrome c were reduced in the hippocampus with MPH (10mg/kg). In conclusion, our results suggest that MPH influences plasticity in the brain of young and adult rats; however, the effects were dependent of age and brain area, on the one hand activating the initial cascade of apoptosis, increasing Bax and reducing Bcl-2, but otherwise inhibiting apoptosis by reduction of caspase-3 and cytochrome c.
哌甲酯（MPH）常用于治疗被诊断患有注意力缺陷多动障碍（ADHD）的儿童；然而，哌甲酯的作用机制尚未完全阐明。研究表明，凋亡信号通路与精神疾病之间存在关联，同时也与这类疾病的治疗靶点有关。因此，我们研究了以1、2和10mg/kg剂量的MPH长期治疗是否会改变幼年和成年Wistar大鼠大脑中促凋亡蛋白Bax、抗凋亡蛋白Bcl-2、半胱天冬酶-3和细胞色素c的水平。我们的结果显示，所有剂量的MPH均使皮质中的Bax增加；MPH（1mg/kg）使Bcl-2和半胱天冬酶-3增加，而MPH（2和10mg/kg）使其减少；所有剂量的MPH治疗后，皮质中的细胞色素c减少；在小脑，所有剂量的MPH均使Bax增加，然而，MPH（2和10mg/kg）使Bcl-2、半胱天冬酶-3和细胞色素c减少；在纹状体，MPH（10mg/kg）治疗使半胱天冬酶-3和细胞色素c减少；MPH（2和10mg/kg）治疗使海马体中的Bax增加，Bcl-2减少；MPH（10mg/kg）使海马体中的半胱天冬酶-3和细胞色素c减少。总之，我们的结果表明，MPH影响幼年和成年大鼠大脑的可塑性；然而，其作用取决于年龄和脑区，一方面激活凋亡的初始级联反应，增加Bax并减少Bcl-2，但另一方面通过减少半胱天冬酶-3和细胞色素c来抑制凋亡。
