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

Fluoxetine restores spatial learning but not accelerated forgetting in mesial temporal lobe epilepsy
Fluoxetine restores spatial learning but not accelerated forgetting in mesial temporal lobe epilepsy
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-dependent learning in patients with mesial temporal lobe epilepsy.
epilepsy, epilepsy memory impairment, neurogenesis, mesial temporal sclerosis, spatial memory
0006-8950
2358-2374
Barkas, Lisa
363cc1b3-078d-48eb-a164-feee7dcd9246
Redhead, Edward
d2342759-2c77-45ef-ac0f-9f70aa5db0df
Taylor, Matthew
13ae9dde-fcce-4e6a-a364-276b4e2ca4de
Shtaya, Anan
15b0b2b2-20db-49bf-aa7f-af49d6e3360f
Hamilton, Derek A.
c65e51ba-fca7-4daa-abfe-ce3a4370fc29
Gray, William P.
f34a0e23-3cba-4b0a-8676-a1b2c3e4c095
Barkas, Lisa
363cc1b3-078d-48eb-a164-feee7dcd9246
Redhead, Edward
d2342759-2c77-45ef-ac0f-9f70aa5db0df
Taylor, Matthew
13ae9dde-fcce-4e6a-a364-276b4e2ca4de
Shtaya, Anan
15b0b2b2-20db-49bf-aa7f-af49d6e3360f
Hamilton, Derek A.
c65e51ba-fca7-4daa-abfe-ce3a4370fc29
Gray, William P.
f34a0e23-3cba-4b0a-8676-a1b2c3e4c095

Barkas, Lisa, Redhead, Edward, Taylor, Matthew, Shtaya, Anan, Hamilton, Derek A. and Gray, William P. (2012) Fluoxetine restores spatial learning but not accelerated forgetting in mesial temporal lobe epilepsy. Brain, 135 (8), 2358-2374. (doi:10.1093/brain/aws176). (PMID:22843410)

Record type: Article

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-dependent learning in patients with mesial temporal lobe epilepsy.

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More information

Published date: August 2012
Keywords: epilepsy, epilepsy memory impairment, neurogenesis, mesial temporal sclerosis, spatial memory
Organisations: Primary Care & Population Sciences, Cognition

Identifiers

Local EPrints ID: 339774
URI: https://eprints.soton.ac.uk/id/eprint/339774
ISSN: 0006-8950
PURE UUID: b6e37c0b-8855-4ade-82b7-add957f9c03a

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Date deposited: 30 May 2012 13:14
Last modified: 19 Jul 2019 21:59

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