www.elsevier.com/locate/brainres Available online at www.sciencedirect.com Research Report Brain apoptosis signaling pathways are regulated by methylphenidate treatment in young and adult rats Gislaine Z. Re ´us a , Giselli Scaini b , Gabriela C. Jeremias b , Camila B. Furlanetto b , Meline O.S. Morais b , Lis Maira Mello-Santos b , Joa ˜ o Quevedo a,c , Emilio L. Streck b,n a 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 b 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 c Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA article info Article history: Accepted 7 August 2014 Keywords: Methylphenidate Bcl-2 Bax Caspase-3 Cytochrome c abstract 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 10 mg/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 (1 mg/kg) and were reduced with MPH (2 and 10 mg/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 10 mg/kg); in the striatum the treatment with MPH (10 mg/kg) decreased caspase-3 and cytochrome c; treatment with MPH (2 and 10 mg/kg) increased Bax and decreased Bcl-2 in the hippocampus; and the caspase-3 and cytochrome c were reduced in the hippocampus with MPH (10 mg/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. & 2014 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.brainres.2014.08.010 0006-8993/& 2014 Elsevier B.V. All rights reserved. n Corresponding author. Fax: þ55 48 3431 2736. E-mail address: est@unesc.net (E.L. Streck). brain research ] ( ]]]] ) ]]] – ]]] Please cite this article as: Réus, G.Z., et al., Brain apoptosis signaling pathways are regulated by methylphenidate treatment in young and adult rats. Brain Research (2014), http://dx.doi.org/10.1016/j.brainres.2014.08.010