Izco, M;
Vettorazzi, A;
Forcen, R;
Blesa, J;
De Toro, M;
Alvarez-Herrera, N;
Cooper, JM;
... Alvarez-Erviti, L; + view all
(2021)
Oral subchronic exposure to the mycotoxin ochratoxin A induces key pathological features of Parkinson's disease in mice six months after the end of the treatment.
Food and Chemical Toxicology
, 152
, Article 112164. 10.1016/j.fct.2021.112164.
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Abstract
Some epidemiological studies with different levels of evidence have pointed to a higher risk of Parkinson's disease (PD) after exposure to environmental toxicants. A practically unexplored potential etiological factor is a group of naturally-occurring fungal secondary metabolites called mycotoxins. The mycotoxin ochratoxin A (OTA) has been reported to be neurotoxic in mice. To further identify if OTA exposure could have a role in PD pathology, Balb/c mice were orally treated with OTA (0.21, 0.5 mg/kg bw) four weeks and left for six months under normal diet. Effects of OTA on the onset, progression of alpha-synuclein pathology and development of motor deficits were evaluated. Immunohistochemical and biochemical analyses showed that oral subchronic OTA treatment induced loss of striatal dopaminergic innervation and dopaminergic cell dysfunction responsible for motor impairments. Phosphorylated alpha-synuclein levels were increased in gut and brain. LAMP-2A protein was decreased in tissues showing alpha-synuclein pathology. Cell cultures exposed to OTA exhibited decreased LAMP-2A protein, impairment of chaperone-mediated autophagy and decreased alpha-synuclein turnover which was linked to miRNAs deregulation, all reminiscent of PD. These results support the hypothesis that oral exposure to low OTA doses in mice can lead to biochemical and pathological changes reported in PD.
| Type: | Article |
|---|---|
| Title: | Oral subchronic exposure to the mycotoxin ochratoxin A induces key pathological features of Parkinson's disease in mice six months after the end of the treatment |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.fct.2021.112164 |
| Publisher version: | https://doi.org/10.1016/j.fct.2021.112164 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | LAMP-2A, Ochratoxin A, Parkinson’s disease, alpha-synuclein, chaperone-mediated autophagy, gut-brain axis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10126231 |
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