Open AccessMethylphenidate Attenuates the Cognitive and Mood Alterations Observed inMbnl2Knockout Mice and Reduces Microglia Overexpression
Author(s) -
Carla RamonDuaso,
Thomas Gener,
Marta Consegal,
Cristina Fernández-Avilés,
Juan Gallego,
Laura Castarlenas,
Maurice S. Swanson,
Rafael de la Torre,
Rafaël Maldonado,
M. Victoria Puig,
Patricia Robledo
Publication year - 2018
Publication title -
cerebral cortex
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.694
H-Index - 250
eISSN - 1460-2199
pISSN - 1047-3211
DOI - 10.1093/cercor/bhy164
Subject(s) - prefrontal cortex , hippocampus , microglia , neuroscience , proinflammatory cytokine , striatum , knockout mouse , dopamine , methylphenidate , psychology , central nervous system , endocrinology , prepulse inhibition , medicine , cognition , attention deficit hyperactivity disorder , inflammation , psychiatry , schizophrenia (object oriented programming) , receptor
Myotonic dystrophy type 1 (DM1) is a multisystem disorder affecting muscle and central nervous system (CNS) function. The cellular mechanisms underlying CNS alterations are poorly understood and no useful treatments exist for the neuropsychological deficits observed in DM1 patients. We investigated the progression of behavioral deficits present in male and female muscleblind-like 2 (Mbnl2) knockout (KO) mice, a rodent model of CNS alterations in DM1, and determined the biochemical and electrophysiological correlates in medial prefrontal cortex (mPFC), striatum and hippocampus (HPC). Male KO exhibited more cognitive impairment and depressive-like behavior than female KO mice. In the mPFC, KO mice showed an overexpression of proinflammatory microglia, increased transcriptional levels of Dat, Drd1, and Drd2, exacerbated dopamine levels, and abnormal neural spiking and oscillatory activities in the mPFC and HPC. Chronic treatment with methylphenidate (MPH) (1 and 3 mg/kg) reversed the behavioral deficits, reduced proinflammatory microglia in the mPFC, normalized prefrontal Dat and Drd2 gene expression, and increased Bdnf and Nrf2 mRNA levels. These findings unravel the mechanisms underlying the beneficial effects of MPH on cognitive deficits and depressive-like behaviors observed in Mbnl2 KO mice, and suggest that MPH could be a potential candidate to treat the CNS deficiencies in DM1 patients.