Neuroprotective and anti-inflammatory roles of the phosphatase and tensin homolog deleted on chromosome Ten (PTEN) Inhibition in a Mouse Model of Temporal Lobe Epilepsy.

Excitotoxic damage represents the major mechanism leading to cell death in many human neurodegenerative diseases such as ischemia, trauma and epilepsy. Caused by an excess of glutamate that acts on metabotropic and ionotropic excitatory receptors, excitotoxicity activates several death signaling pat...

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Main Authors: Valentina Grande, Giusi Manassero, Alessandro Vercelli
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4264755?pdf=render
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spelling doaj-fbd9400a992b452abe2c61546c8846952020-11-24T20:49:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01912e11455410.1371/journal.pone.0114554Neuroprotective and anti-inflammatory roles of the phosphatase and tensin homolog deleted on chromosome Ten (PTEN) Inhibition in a Mouse Model of Temporal Lobe Epilepsy.Valentina GrandeGiusi ManasseroAlessandro VercelliExcitotoxic damage represents the major mechanism leading to cell death in many human neurodegenerative diseases such as ischemia, trauma and epilepsy. Caused by an excess of glutamate that acts on metabotropic and ionotropic excitatory receptors, excitotoxicity activates several death signaling pathways leading to an extensive neuronal loss and a consequent strong activation of astrogliosis. Currently, the search for a neuroprotective strategy is aimed to identify the level in the signaling pathways to block excitotoxicity avoiding the loss of important physiological functions and side effects. To this aim, PTEN can be considered an ideal candidate: downstream the excitatory receptors activated in excitotoxicity (whose inhibition was shown to be not clinically viable), it is involved in neuronal damage and in the first stage of the reactive astrogliosis in vivo. In this study, we demonstrated the involvement of PTEN in excitotoxicity through its pharmacological inhibition by dipotassium bisperoxo (picolinato) oxovanadate [bpv(pic)] in a model of temporal lobe epilepsy, obtained by intraperitoneal injection of kainate in 2-month-old C57BL/6J male mice. We have demonstrated that inhibition of PTEN by bpv(pic) rescues neuronal death and decreases the reactive astrogliosis in the CA3 area of the hippocampus caused by systemic administration of kainate. Moreover, the neurotoxin administration increases significantly the scanty presence of mitochondrial PTEN that is significantly decreased by the administration of the inhibitor 6 hr after the injection of kainate, suggesting a role of PTEN in mitochondrial apoptosis. Taken together, our results confirm the key role played by PTEN in the excitotoxic damage and the strong anti-inflammatory and neuroprotective potential of its inhibition.http://europepmc.org/articles/PMC4264755?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Valentina Grande
Giusi Manassero
Alessandro Vercelli
spellingShingle Valentina Grande
Giusi Manassero
Alessandro Vercelli
Neuroprotective and anti-inflammatory roles of the phosphatase and tensin homolog deleted on chromosome Ten (PTEN) Inhibition in a Mouse Model of Temporal Lobe Epilepsy.
PLoS ONE
author_facet Valentina Grande
Giusi Manassero
Alessandro Vercelli
author_sort Valentina Grande
title Neuroprotective and anti-inflammatory roles of the phosphatase and tensin homolog deleted on chromosome Ten (PTEN) Inhibition in a Mouse Model of Temporal Lobe Epilepsy.
title_short Neuroprotective and anti-inflammatory roles of the phosphatase and tensin homolog deleted on chromosome Ten (PTEN) Inhibition in a Mouse Model of Temporal Lobe Epilepsy.
title_full Neuroprotective and anti-inflammatory roles of the phosphatase and tensin homolog deleted on chromosome Ten (PTEN) Inhibition in a Mouse Model of Temporal Lobe Epilepsy.
title_fullStr Neuroprotective and anti-inflammatory roles of the phosphatase and tensin homolog deleted on chromosome Ten (PTEN) Inhibition in a Mouse Model of Temporal Lobe Epilepsy.
title_full_unstemmed Neuroprotective and anti-inflammatory roles of the phosphatase and tensin homolog deleted on chromosome Ten (PTEN) Inhibition in a Mouse Model of Temporal Lobe Epilepsy.
title_sort neuroprotective and anti-inflammatory roles of the phosphatase and tensin homolog deleted on chromosome ten (pten) inhibition in a mouse model of temporal lobe epilepsy.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2014-01-01
description Excitotoxic damage represents the major mechanism leading to cell death in many human neurodegenerative diseases such as ischemia, trauma and epilepsy. Caused by an excess of glutamate that acts on metabotropic and ionotropic excitatory receptors, excitotoxicity activates several death signaling pathways leading to an extensive neuronal loss and a consequent strong activation of astrogliosis. Currently, the search for a neuroprotective strategy is aimed to identify the level in the signaling pathways to block excitotoxicity avoiding the loss of important physiological functions and side effects. To this aim, PTEN can be considered an ideal candidate: downstream the excitatory receptors activated in excitotoxicity (whose inhibition was shown to be not clinically viable), it is involved in neuronal damage and in the first stage of the reactive astrogliosis in vivo. In this study, we demonstrated the involvement of PTEN in excitotoxicity through its pharmacological inhibition by dipotassium bisperoxo (picolinato) oxovanadate [bpv(pic)] in a model of temporal lobe epilepsy, obtained by intraperitoneal injection of kainate in 2-month-old C57BL/6J male mice. We have demonstrated that inhibition of PTEN by bpv(pic) rescues neuronal death and decreases the reactive astrogliosis in the CA3 area of the hippocampus caused by systemic administration of kainate. Moreover, the neurotoxin administration increases significantly the scanty presence of mitochondrial PTEN that is significantly decreased by the administration of the inhibitor 6 hr after the injection of kainate, suggesting a role of PTEN in mitochondrial apoptosis. Taken together, our results confirm the key role played by PTEN in the excitotoxic damage and the strong anti-inflammatory and neuroprotective potential of its inhibition.
url http://europepmc.org/articles/PMC4264755?pdf=render
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