title: Enrichment and training improve cognition in rats with cortical malformations.
abstract: Children with malformations of cortical development (MCD) frequently have associated cognitive impairments which reduce quality of life. We hypothesized that cognitive deficits associated with MCD can be improved with environmental manipulation or additional training. The E17 methylazoxymethanol acetate (MAM) exposure model bears many anatomical hallmarks seen in human MCDs as well as similar behavioral and cognitive deficits. We divided control and MAM exposed Sprague-Dawley rats into enriched and non-enriched groups and tested performance in the Morris water maze. Another group similarly divided underwent sociability testing and also underwent Magnetic Resonance Imaging (MRI) scans pre and post enrichment. A third group of control and MAM rats without enrichment were trained until they reached criterion on the place avoidance task. MAM rats had impaired performance on spatial tasks and enrichment improved performance of both control and MAM animals. Although MAM rats did not have a deficit in sociability they showed similar improvement with enrichment as controls. MRI revealed a whole brain volume decrease with MAM exposure, and an increase in both MAM and control enriched volumes in comparison to non-enriched animals. In the place avoidance task, MAM rats required approximately 3 times as long to reach criterion as control animals, but with additional training were able to reach control performance. Environmental manipulation and additional training can improve cognition in a rodent MCD model. We therefore suggest that patients with MCD may benefit from appropriate alterations in educational strategies, social interaction and environment. These factors should be considered in therapeutic strategies.
authors.affiliation: Department of Neurology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States of America.
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Jenks
authors.affiliation: Department of Neurology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States of America.
authors.forename: Marcella M
authors.initials: MM
authors.lastname: Lucas
authors.affiliation: Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London, United Kingdom.
authors.forename: Ben A
authors.initials: BA
authors.lastname: Duffy
authors.affiliation: Department of Neurology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States of America.
authors.forename: Ashlee A
authors.initials: AA
authors.lastname: Robbins
authors.affiliation: Department of Radiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States of America.
authors.forename: Barjor
authors.initials: B
authors.lastname: Gimi
authors.affiliation: Department of Neurology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States of America.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Barry
authors.affiliation: Department of Neurology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States of America ; University College London, Institute of Child Health, London, United Kingdom.
authors.forename: Rod C
authors.initials: RC
authors.lastname: Scott
mesh_terms: D000818:Animals; D001362:Avoidance Learning; D001522:Behavior, Animal; D002755:Choice Behavior; D003071:Cognition; D003213:Conditioning, Psychological; D005260:Female; D008279:Magnetic Resonance Imaging; D008297:Male; D054220:Malformations of Cortical Development / Q000139:chemically induced / Q000175:diagnosis / Q000523:psychology*; D018782:Maze Learning; D008746:Methylazoxymethanol Acetate / Q000008:administration & dosage / Q000009:adverse effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats
chemical_list: D008746:Methylazoxymethanol Acetate