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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
- Source :
- PLoS ONE, PLoS ONE, Vol 9, Iss 12, p e114554 (2014)
- Publication Year :
- 2014
- Publisher :
- Public Library of Science (PLoS), 2014.
-
Abstract
- 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.
- Subjects :
- Male
PTEN
hippocampus
Anti-Inflammatory Agents
Excitotoxicity
lcsh:Medicine
Kainate receptor
medicine.disease_cause
Nervous System
Mice
chemistry.chemical_compound
Neural Pathways
Tensin
Enzyme Inhibitors
lcsh:Science
Neurons
Kainic Acid
Multidisciplinary
Cell Death
Neuronal Morphology
biology
Glutamate receptor
CA3 Region, Hippocampal
Mitochondria
Astrogliosis
Protein Transport
Neuroprotective Agents
astrogliosis
epilepsy
cell deah
Anatomy
Signal Transduction
Research Article
Kainic acid
Neurotoxins
Nerve Tissue Proteins
Neuroprotection
Glial Fibrillary Acidic Protein
medicine
Animals
lcsh:R
JNK Mitogen-Activated Protein Kinases
PTEN Phosphohydrolase
Biology and Life Sciences
Phosphoproteins
medicine.disease
Mice, Inbred C57BL
Disease Models, Animal
Neuroanatomy
Epilepsy, Temporal Lobe
chemistry
Cellular Neuroscience
Immunology
Cancer research
biology.protein
lcsh:Q
Molecular Neuroscience
Neuroscience
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....15edf7220827e7246ea79047cd4ab3d7