Altered Expression of Astrocyte-Related Receptors and Channels Correlates With Epileptogenesis in Hippocampal Sclerosis.
Adolescent
Adult
Astrocytes
/ metabolism
Biomarkers
/ metabolism
Case-Control Studies
Child
Child, Preschool
Epilepsy
/ etiology
Hippocampus
/ metabolism
Humans
Immunoblotting
Immunohistochemistry
Male
Potassium Channels
/ metabolism
Receptors, Metabotropic Glutamate
/ metabolism
Receptors, Purinergic P2Y
/ metabolism
Sclerosis
Signal Transduction
Up-Regulation
Young Adult
astrocyte
epilepsy
hippocampal sclerosis
metabotropic receptor
potassium channels
purinergic receptor
Journal
Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society
ISSN: 1615-5742
Titre abrégé: Pediatr Dev Pathol
Pays: United States
ID NLM: 9809673
Informations de publication
Date de publication:
Historique:
pubmed:
6
6
2019
medline:
28
4
2020
entrez:
6
6
2019
Statut:
ppublish
Résumé
Hippocampal sclerosis (HS) is one of the major causes of intractable epilepsy. Astrogliosis in epileptic brain is a peculiar condition showing epileptogenesis and is thought to be different from the other pathological conditions. The aim of this study is to investigate the altered expression of astrocytic receptors, which contribute to neurotransmission in the synapse, and channels in HS lesions. We performed immunohistochemical and immunoblotting analyses of the P2RY1, P2RY2, P2RY4, Kir4.1, Kv4.2, mGluR1, and mGluR5 receptors and channels with the brain samples of 20 HS patients and 4 controls and evaluated the ratio of immunopositive cells and those expression levels. The ratio of each immunopositive cell per glial fibrillary acidic protein-positive astrocytes and the expression levels of all 7 astrocytic receptors and channels in HS lesions were significantly increased. We previously described unique astrogliosis in epileptic lesions similar to what was observed in this study. This phenomenon is considered to trigger activation of the related signaling pathways and then contribute to epileptogenesis. Thus, astrocytes in epileptic lesion may show self-hyperexcitability and contribute to epileptogenesis through the endogenous astrocytic receptors and channels. These findings may suggest novel astrocytic receptor-related targets for the pharmacological treatment of epilepsy.
Sections du résumé
BACKGROUND
BACKGROUND
Hippocampal sclerosis (HS) is one of the major causes of intractable epilepsy. Astrogliosis in epileptic brain is a peculiar condition showing epileptogenesis and is thought to be different from the other pathological conditions. The aim of this study is to investigate the altered expression of astrocytic receptors, which contribute to neurotransmission in the synapse, and channels in HS lesions.
METHODS
METHODS
We performed immunohistochemical and immunoblotting analyses of the P2RY1, P2RY2, P2RY4, Kir4.1, Kv4.2, mGluR1, and mGluR5 receptors and channels with the brain samples of 20 HS patients and 4 controls and evaluated the ratio of immunopositive cells and those expression levels.
RESULTS
RESULTS
The ratio of each immunopositive cell per glial fibrillary acidic protein-positive astrocytes and the expression levels of all 7 astrocytic receptors and channels in HS lesions were significantly increased. We previously described unique astrogliosis in epileptic lesions similar to what was observed in this study.
CONCLUSION
CONCLUSIONS
This phenomenon is considered to trigger activation of the related signaling pathways and then contribute to epileptogenesis. Thus, astrocytes in epileptic lesion may show self-hyperexcitability and contribute to epileptogenesis through the endogenous astrocytic receptors and channels. These findings may suggest novel astrocytic receptor-related targets for the pharmacological treatment of epilepsy.
Identifiants
pubmed: 31166880
doi: 10.1177/1093526619855488
doi:
Substances chimiques
Biomarkers
0
Potassium Channels
0
Receptors, Metabotropic Glutamate
0
Receptors, Purinergic P2Y
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM