URV researchers are taking part in a pioneering study that analyses the behavioural and molecular effects in the short, medium and long term resulting from exposure to chlorpyrifos, which may be related to hyperactivity, autism and addictions

Chlorpyrifos (CPF) is one of the most commonly used pesticides in the world, and also one of the most questioned because of its toxic effects on health. Despite the evidence of its potential effects on development it is still permitted for agricultural uses in Europe and the United States, while it has been prohibited in countries such as Thailand. Now a study carried out by researchers from the Research Centre for Neurobehaviour and Health (NEUROLAB), the URV’s Research Centre for Behaviour Assessment and a research group from the Research Centre in Health (CEINSA) of the University of Amería sheds more light on the harm done by exposure to this pesticide at low doses. Among the main conclusions of the study, the researchers have found that exposure to CPF can have neurotoxic effects related to hyperactivity, autism and addictions, and on learning and memory. It is a pioneering study on the behavioural and molecular effects of exposure to this pesticide in the short, medium and long term.

The researchers administered low doses of the compound to newborn rats and mice, a stage in life in which the development of the central nervous system is similar to that of humans in the last weeks of gestation and the first weeks after birth. Although the model is ideal, at present this period of development is one of the least studied in terms of exposure to CPF.

The authors found that exposure during this period induced anomalous behaviours that are normally observed in various psychiatric and neurological pathologies such as an increase in motor activity in adolescence (associated with attention deficit disorder with hyperactivity), an increase in impulsive responses (associated such different pathologies as autism or addictions) or a progressive decrease in motor functions with age (associated with neurodegenerative pathologies such as Parkinson’s Disease).

Through neuropsychopharmacological studies the authors have also found that this exposure modified the cholinergic system, one of the main neurotransmission systems of the central nervous system, the progressive degradation of which is one of the leading physiopathological correlates of Alzheimer. This finding is in line with other studies on humans that relate exposure to pesticide compounds with this disease.

The authors of the study also analysed several molecular markers and observed that exposure affected the levels of expression of various genes in specific areas of the brain, altered the composition of the intestinal microbiota at different ages and induced selective alterations in the levels of some metabolites in the blood that are essential for the organism to function correctly, specifically in females.

“In the laboratory we have been working for some time now with a model of transgenic mice that have a human gene – APOE3 or APOE4 – which is known to make them vulnerable to some diseases. We have found that both genotype and sex have a different effect on sensitivity to the toxic components of the pesticide, and whether exposure takes place prenatally, shortly after birth or in adulthood is also important,” says Maria Teresa Colomina, a member of the NEUROLAB research group.

This research has involved a multidisciplinary team that includes experts in behaviour and neuropsychopharmacology as well as specialists in molecular biology and chemical sciences. The URV members Maria Teresa Colomina, Maria Cabré, Laia Guàrdia, Judit Biosca and Jordi Blanco and a team from the University of Almería led the project, which was funded by the Spanish Ministry of Economy and Competitiveness and the European Fund for Regional Development: PSI2017-86847-C2-1-R MINECO-FEDER i PSI2017-86847-C2-2-R.

Reference: Guardia-Escote L, Basaure P, Biosca-Brull J, Cabré M, Blanco J, Pérez-Fernández C, Sánchez-Santed F, Domingo JL, Colomina MT. APOE genotype and postnatal chlorpyrifos exposure modulate gut microbiota and cerebral short-chain fatty acids in preweaning mice. Food Chem Toxicol. 2020 Jan;135:110872. doi: 10.1016/j.fct.2019.110872.

Perez-Fernandez C, Morales-Navas M, Guardia-Escote L, Garrido-Cárdenas JA, Colomina MT, Giménez E, Sánchez-Santed F. Long-term effects of low doses of Chlorpyrifos exposure at the preweaning developmental stage: A locomotor, pharmacological, brain gene expression and gut microbiome analysis. Food Chem Toxicol. 2020 Jan;135:110865. doi: 10.1016/j.fct.2019.110865.