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Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons
Published on: November 6, 2017
Ochratoxin A induces apoptosis in neuronal cells
Xiangnan Zhang1, Christine Boesch-Saadatmandi, Yijia Lou
1Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 310058, Hangzhou, China.
Genes & Nutrition
|January 17, 2009
Summary
The mycotoxin ochratoxin A (OTA) causes neurotoxicity by inducing apoptosis in neurons. This finding suggests OTA may contribute to neurodegenerative diseases like Alzheimer's and Parkinson's.
Area of Science:
- Neuroscience
- Toxicology
- Cell Biology
Background:
- Ochratoxin A (OTA) is a common food contaminant with known nephrotoxic and hepatotoxic effects.
- Potential neurotoxic effects of OTA are not well understood.
- Apoptosis is implicated in the pathogenesis of neurodegenerative diseases.
Purpose of the Study:
- To investigate the neurotoxic potential of Ochratoxin A (OTA) in neuronal cells.
- To elucidate the mechanisms underlying OTA-induced neurotoxicity, focusing on apoptosis.
Main Methods:
- Primary neurons and SH-SY5Y neuronal cells were exposed to varying concentrations of OTA (0.1-2.5 mumol/L).
- Cytotoxicity, caspase activation (caspase-9 and caspase-3), and mitochondrial membrane potential were assessed.
- The effect of caspase inhibitors on OTA-induced neurocytotoxicity was evaluated.
Main Results:
- OTA exposure led to a dose-dependent increase in cytotoxicity in both neuronal cell types.
- Caspase-9 and caspase-3 activation was observed following OTA treatment.
- OTA-induced apoptosis was associated with a loss of mitochondrial membrane potential.
- Caspase inhibitors partially protected against OTA-induced neurocytotoxicity.
Conclusions:
- Ochratoxin A exhibits neurotoxic effects at relatively low concentrations.
- OTA-induced neurotoxicity is, at least partly, mediated by apoptosis.
- OTA may play a role in the pathogenesis of neurodegenerative diseases involving apoptotic processes, such as Alzheimer's and Parkinson's disease.
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