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Fluoxetine restores spatial learning but not accelerated forgetting in mesial temporal lobe epilepsy

Barkas, Lisa, Redhead, Edward, Taylor, Matthew, Shtaya, Anan, Hamilton, Derek A. and Gray, William Peter 2012. Fluoxetine restores spatial learning but not accelerated forgetting in mesial temporal lobe epilepsy. Brain: a Journal of Neurology 135 (8) , pp. 2358-2374. 10.1093/brain/aws176

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Abstract

Learning and memory dysfunction is the most common neuropsychological effect of mesial temporal lobe epilepsy, and because the underlying neurobiology is poorly understood, there are no pharmacological strategies to help restore memory function in these patients. We have demonstrated impairments in the acquisition of an allocentric spatial task, in patients with unilateral hippocampal sclerosis. We also show that patients have accelerated forgetting of the learned spatial task and that this is associated with damage to the non-dominant hippocampal formation. We go on to show a very similar pattern of chronic allocentric learning and accelerated forgetting in a status epilepticus model of mesial temporal lobe epilepsy in rats, which is associated with reduced and abnormal hippocampal neurogenesis. Finally, we show that reversal of the neurogenic deficit using fluoxetine is associated with reversal of the learning deficit but not the accelerated forgetting, pointing to a possible dissociation in the underlying mechanisms, as well as a potential therapeutic strategy for improving hippocampal-dependant learning in patients with mesial temporal lobe epilepsy.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: Epilepsy; Epilepsy memory impairment; Neurogenesis; Mesial temporal sclerosis; Spatial memory
Publisher: Oxford University Press
ISSN: 0006-8950
Last Modified: 04 Jun 2017 04:22
URI: http://orca-mwe.cf.ac.uk/id/eprint/37560

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