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.
Highlights
Malformations of Cortical Development (MCD) are a wide range of disorders with many genetic and environmental causes [1,2]
In a series of experiments, we show that methylazoxymethanol acetate (MAM) treated animals are impaired in two spatial tasks in comparison to controls, that enrichment improved spatial cognition and that additional training allows animals with MCD to reach control levels of behavior on a spatial task
We contend that children with MCD associated learning and behavioral impairments and seizures often have restrictions placed on their environments and educational access
Summary
Malformations of Cortical Development (MCD) are a wide range of disorders with many genetic and environmental causes [1,2]. MCD is a term used to group together disruptions in brain development caused by a failure in neuronal migration or neuronal development. MCD’s are frequently associated with epilepsy, developmental delay, and psychiatric impairments such as schizophrenia [3]. In addition to cognitive effects, there is an important link between MCD and childhood epilepsy. Forty percent of children with refractory epilepsy are estimated to have an underlying cortical malformation [4]. Children with MCD and epilepsy face a potentially crippling additive effect wherein both conditions simultaneously and independently contribute to developmental delay and cognitive impairment.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
