In vitro study of ochratoxin A in the expression of genes associated with neuron survival and viability

Riddhi Sharma, Sean M. Gettings, Gareth Hazell, Nora Bourbia

Research output: Contribution to journalArticlepeer-review

7 Citations (SciVal)

Abstract

Ochratoxin A (OTA) is a common mycotoxin and known contaminant of crops, foods and drinks. As OTA crosses the blood-brain barrier, this study investigated the role of OTA, as an environmental hazard, on neuronal survival and viability. The impact of a range of OTA concentrations on the expression of MAPT, BAX, P53, BDNF and TPPP genes was investigated using human neuroblastoma (SH-SY5Y) cells. The absence of altered gene expression determined using reverse transcription quantitative PCR demonstrated that exposure to a typical daily dose of OTA delivered to the brain (2 fM), may not trigger neuronal dysfunction. However, a dose of OTA (2 pM) decreased BDNF expression. BDNF and TPPP expression were significantly reduced after 1 day and significantly increased after 2 days of exposure to 1 µM OTA. The expression of P53, MAPT, and BAX was reduced at both days. Thus, despite OTA cytotoxicity, SH-SY5Y cells entered a survival state following a strong toxic insult. A typical daily environmental OTA exposure does not appear to carry an increased risk of neurodegenerative disease. However, BDNF dysfunction may occur through prolonged exposure to a dose one thousand times higher than the typical daily consumed OTA dose potentially causing adverse effects on neuronal health.

Original languageEnglish
Article number153376
JournalToxicology
Volume483
Early online date15 Nov 2022
DOIs
Publication statusPublished - 1 Jan 2023
Externally publishedYes

Bibliographical note

Funding Information:
This study is funded by the National Institute for Health Research (NIHR) Health Protection Research Unit in Chemical and Radiation Threats and Hazards, a partnership between UK Health Security Agency and Imperial College London ( NIHR200922 ). The views expressed are those of the author(s) and not necessarily those of the NIHR, UK Health Security Agency or the Department of Health and Social Care.

Keywords

  • BDNF
  • Mycotoxin
  • Neuron
  • Ochratoxin A
  • SH-SY5Y
  • Survival

ASJC Scopus subject areas

  • Toxicology

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