Long-Term Fipronil Treatment Induces Hyperactivity in Female Mice.

Svenja Koslowski,Pierrïck Auvray,Camille Latapy,Marc Blondel,Laurent Meijer

doi:10.3390/ijerph17051579

Abstract

Fipronil is an insecticide widely used for veterinary and agricultural purposes. While its insecticidal properties mostly rely on its high affinity antagonistic activity on insect γ aminobutyric acid (GABA) receptors, fipronil and its main metabolite fipronil sulfone nevertheless display non-negligible affinity for mammalian GABAA receptor. As several environmental toxicants have been shown to raise the risk of developing various neurodegenerative disorders, the aim of this study was to evaluate whether long-term low dose administration of fipronil could lead to cognitive deficiencies. Our results indicate that long-term fipronil treatment leads to behavioral perturbations in mice, indicating an accumulative effect of sustained exposure to low dose of fipronil. Although no memory impairment was observed during the course of our study, we noticed a significant hyperlocomotion behavior after 43 weeks of weekly fipronil administration, which is consistent with its direct effect on the GABAergic system.

Highlights

Dementia is an increasing problem in Western countries, given that aging is a major risk factor for developing this type of impairment [1,2]
One of the fipronil-treated mice had to be sacrificed for ethical reasons in the 18th week of the study
At 1/9 of the LD50 determined for single oral administration in mice (91 mg/kg; [28]), animals chronically treated over a long period of timeinby fipronil showed no sign of toxicity

Summary

Introduction

Dementia is an increasing problem in Western countries, given that aging is a major risk factor for developing this type of impairment [1,2]. As human life expectancy increases, dementia develops as a major problem. In 2018, over 50 million people lived with dementia worldwide and in 2015 it was estimated that more than 9.9 million new cases arise every year [3,4]. In addition to representing a major issue for public health, dementia has a profound financial impact, as worldwide societal economic costs related to care for dementia patients were estimated to USD 818 billion in 2015 [4]. Aged-related dementia can most commonly be related to neurodegenerative diseases, the most frequent one being Alzheimer’s disease (AD). Recent studies carried out on dementia patients in Sweden and

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