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Wortmannin Attenuates Seizure-Induced Hyperactive PI3K/Akt/mTOR Signaling, Impaired Memory, and Spine Dysmorphology in Rats

Numerous studies have shown epilepsy-associated cognitive deficits, but less is known about the effects of one single generalized seizure. Recent studies demonstrate that a single, self-limited seizure can result in memory deficits and induces hyperactive phosphoinositide 3-kinase/Akt (protein kinas...

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Autores principales: Carter, Angela N., Born, Heather A., Levine, Amber T., Dao, An T., Zhao, Amanda J., Lee, Wai L., Anderson, Anne E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society for Neuroscience 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467399/
https://www.ncbi.nlm.nih.gov/pubmed/28612047
http://dx.doi.org/10.1523/ENEURO.0354-16.2017
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author Carter, Angela N.
Born, Heather A.
Levine, Amber T.
Dao, An T.
Zhao, Amanda J.
Lee, Wai L.
Anderson, Anne E.
author_facet Carter, Angela N.
Born, Heather A.
Levine, Amber T.
Dao, An T.
Zhao, Amanda J.
Lee, Wai L.
Anderson, Anne E.
author_sort Carter, Angela N.
collection PubMed
description Numerous studies have shown epilepsy-associated cognitive deficits, but less is known about the effects of one single generalized seizure. Recent studies demonstrate that a single, self-limited seizure can result in memory deficits and induces hyperactive phosphoinositide 3-kinase/Akt (protein kinase B)/mechanistic target of rapamycin (PI3K/Akt/mTOR) signaling. However, the effect of a single seizure on subcellular structures such as dendritic spines and the role of aberrant PI3K/Akt/mTOR signaling in these seizure-induced changes are unclear. Using the pentylenetetrazole (PTZ) model, we induced a single generalized seizure in rats and: (1) further characterized short- and long-term hippocampal and amygdala-dependent memory deficits, (2) evaluated whether there are changes in dendritic spines, and (3) determined whether inhibiting hyperactive PI3K/Akt/mTOR signaling rescued these alterations. Using the PI3K inhibitor wortmannin (Wort), we partially rescued short- and long-term memory deficits and altered spine morphology. These studies provide evidence that pathological PI3K/Akt/mTOR signaling plays a role in seizure-induced memory deficits as well as aberrant spine morphology.
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spelling pubmed-54673992017-06-13 Wortmannin Attenuates Seizure-Induced Hyperactive PI3K/Akt/mTOR Signaling, Impaired Memory, and Spine Dysmorphology in Rats Carter, Angela N. Born, Heather A. Levine, Amber T. Dao, An T. Zhao, Amanda J. Lee, Wai L. Anderson, Anne E. eNeuro New Research Numerous studies have shown epilepsy-associated cognitive deficits, but less is known about the effects of one single generalized seizure. Recent studies demonstrate that a single, self-limited seizure can result in memory deficits and induces hyperactive phosphoinositide 3-kinase/Akt (protein kinase B)/mechanistic target of rapamycin (PI3K/Akt/mTOR) signaling. However, the effect of a single seizure on subcellular structures such as dendritic spines and the role of aberrant PI3K/Akt/mTOR signaling in these seizure-induced changes are unclear. Using the pentylenetetrazole (PTZ) model, we induced a single generalized seizure in rats and: (1) further characterized short- and long-term hippocampal and amygdala-dependent memory deficits, (2) evaluated whether there are changes in dendritic spines, and (3) determined whether inhibiting hyperactive PI3K/Akt/mTOR signaling rescued these alterations. Using the PI3K inhibitor wortmannin (Wort), we partially rescued short- and long-term memory deficits and altered spine morphology. These studies provide evidence that pathological PI3K/Akt/mTOR signaling plays a role in seizure-induced memory deficits as well as aberrant spine morphology. Society for Neuroscience 2017-06-12 /pmc/articles/PMC5467399/ /pubmed/28612047 http://dx.doi.org/10.1523/ENEURO.0354-16.2017 Text en Copyright © 2017 Carter et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle New Research
Carter, Angela N.
Born, Heather A.
Levine, Amber T.
Dao, An T.
Zhao, Amanda J.
Lee, Wai L.
Anderson, Anne E.
Wortmannin Attenuates Seizure-Induced Hyperactive PI3K/Akt/mTOR Signaling, Impaired Memory, and Spine Dysmorphology in Rats
title Wortmannin Attenuates Seizure-Induced Hyperactive PI3K/Akt/mTOR Signaling, Impaired Memory, and Spine Dysmorphology in Rats
title_full Wortmannin Attenuates Seizure-Induced Hyperactive PI3K/Akt/mTOR Signaling, Impaired Memory, and Spine Dysmorphology in Rats
title_fullStr Wortmannin Attenuates Seizure-Induced Hyperactive PI3K/Akt/mTOR Signaling, Impaired Memory, and Spine Dysmorphology in Rats
title_full_unstemmed Wortmannin Attenuates Seizure-Induced Hyperactive PI3K/Akt/mTOR Signaling, Impaired Memory, and Spine Dysmorphology in Rats
title_short Wortmannin Attenuates Seizure-Induced Hyperactive PI3K/Akt/mTOR Signaling, Impaired Memory, and Spine Dysmorphology in Rats
title_sort wortmannin attenuates seizure-induced hyperactive pi3k/akt/mtor signaling, impaired memory, and spine dysmorphology in rats
topic New Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467399/
https://www.ncbi.nlm.nih.gov/pubmed/28612047
http://dx.doi.org/10.1523/ENEURO.0354-16.2017
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