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Updated: Sep 20, 2026

Hippocampal Neuronal Cultures to Detect and Study New Pathogenic Antibodies Involved in Autoimmune Encephalitis
Published on: June 2, 2022
Anti-porin antibodies prevent excitotoxic and ischemic damage to brain tissue
Jose L Perez Velazquez1, Larisa Kokarovtseva, Michael Weisspapir
1The Hospital for Sick Children, Brain and Behaviour Programme, Department of Paediatrics, University of Toronto, Toronto, Canada. jlpv@sickkids.ca
Abstract:
The mitochondrial permeability transition (MPT) is a converging event for different molecular routes leading to cellular death after excitotoxic/oxidative stress, and is considered to represent the opening of a pore in the mitochondrial membrane. There is evidence that the outer mitochondrial membrane protein porin is involved in the MPT and apoptosis. We present here a proof-of-principle study to address the hypothesis that anti-porin antibodies can prevent excitotoxic/ischemia-induced cell death. We generated anti-porin antibodies and show that the F(ab)(2) fragments penetrate living cells, reduce Ca(2+)-induced mitochondrial swelling as other MPT blockers do, and decrease neuronal death in dissociated and organotypic brain slice cultures exposed to excitotoxic and ischemic episodes. These observations present direct evidence that anti-porin antibody fragments prevent cell damage in brain tissue, that porin is a crucial protein involved in mitochondrial and cell dysfunction, and that it is conceivable that antibodies can be used as therapeutic agents.
Insights
Anti-porin antibodies prevent cell death caused by excitotoxicity and ischemia. These antibody fragments target porin, a mitochondrial protein, offering a potential new therapeutic strategy for neurodegenerative diseases.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Mitochondrial permeability transition (MPT) is a key event in cell death pathways following excitotoxic/oxidative stress.
- Porin, an outer mitochondrial membrane protein, is implicated in MPT and apoptosis.
Purpose of the Study:
- To test if anti-porin antibodies can prevent cell death induced by excitotoxicity and ischemia.
- To investigate the role of porin in neuronal death.
Main Methods:
- Generation of anti-porin antibodies.
- Testing F(ab)(2) antibody fragments for cell penetration and reduction of calcium-induced mitochondrial swelling.
- Evaluating the effect of antibody fragments on neuronal death in dissociated and organotypic brain slice cultures subjected to excitotoxic and ischemic conditions.
Main Results:
- Anti-porin antibody fragments successfully penetrated living cells.
- These fragments reduced calcium-induced mitochondrial swelling, similar to other MPT blockers.
- Significant decrease in neuronal death was observed in brain cultures exposed to excitotoxic and ischemic insults.
Conclusions:
- Anti-porin antibody fragments effectively prevent cell damage in brain tissue.
- Porin plays a critical role in mitochondrial dysfunction and subsequent cell death.
- Antibodies represent a potential therapeutic approach for treating conditions involving excitotoxicity and ischemia.
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