Chronic Administration of Fipronil Heterogeneously Alters the Neurochemistry of Monoaminergic Systems in the Rat Brain

Abstract

Fipronil (FPN), a widely used pesticide for agricultural and non-agricultural pest control, is possibly neurotoxic for mammals. Brain monoaminergic systems, involved in virtually all brain functions, have been shown to be sensitive to numerous pesticides. Here, we addressed the hypothesis that chronic exposure to FPN could modify brain monoamine neurochemistry. FPN (10 mg/kg) was chronically administered for 21 days through oral gavage in rats. Thereafter, the tissue concentrations of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid; serotonin (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA); and noradrenaline (NA) were measured in 30 distinct brain regions. FPN significantly decreased DA and its metabolite levels in most striatal territories, including the nucleus accumbens and the substantia nigra (SN). FPN also diminished 5-HT levels in some striatal regions and the SN. The indirect index of the turnovers, DOPAC/DA and 5-HIAA/5-HT ratios, was increased in numerous brain regions. FPN reduced the NA content only in the nucleus accumbens core. Using the Bravais–Pearson test to study the neurochemical organization of monoamines through multiple correlative analyses across the brain, we found fewer correlations for NA, DOPAC/DA, and 5-HIAA/5-HT ratios, and an altered pattern of correlations within and between monoamine systems. We therefore conclude that the chronic administration of FPN in rats induces massive and inhomogeneous changes in the DA and 5-HT systems in the brain.

Simulated Microgravity Subtlety Changes Monoamine Function across the Rat Brain

“…The correlograms for NA, DA, and 5-HT elaborated for CTL and SMG groups are reported in Figure 6. As expected from previous works [28,33], the number of correlations across the brain for one monoamine was low. For NA, 33 correlations were found in CTL, five of them involving the LC with other brain regions (Figure 6A).…”

“…One advantage of performing correlative analyses is to address in a single brain region the relationship between the compounds of homologous systems, for instance, DOPAC vs. DA content, and presumably heterologous compounds, such as NA and DOPAC. In our growing experience of this type of analysis [26,28,29,33], although performed in strains and species other than Long Evans rats, the relationship between NA and the DA metabolites in several brain regions is usually lower than that reported in the present experiment. First, we found some correlations between NA and the DA metabolites that could be related to our "control" conditions (see below), and second, the number of these "heterologous" correlations increased in the SMG group.…”

“…Meanwhile, it is likely that the isolation, although operating for a small period, could alter the responsiveness of monoaminergic systems [57,58]). It could already impact the relationship between the NA and DA systems we exemplified above, as well as the levels of correlations of the ratio 5-HIAA/5-HT that was found to be higher in the control groups of other experiments [26,33].…”

Influence of energy deficiency on the subcellular processes of Substantia Nigra Pars Compacta cell for understanding Parkinsonian neurodegeneration

“…Using cellular models 174 , monitoring the mitochondrial calcium, ATP, NADPH, pH, membrane potential, oxygen consumption rate, ROS production, and morphology gives a better understanding of mitochondrial bioenergetic function in the neuron under energy deficits, oxidative stress, and excitotoxicity 4 , 174 – 176 . During progressive energy deficiency, DA and its metabolites can be measured to check for production of ROS leading to oxidative stress in the neuron using toxin-induced animal pathological models 177 , 178 .…”

Is the Exposome Involved in Brain Disorders through the Serotoninergic System?

“…Increases in both serotonin and 5-HIAA content, and only in serotonin content, were detected in the hypothalamus and the preoptic area of chlordecone-treated female rats, respectively [33]. The chronic administration of fipronil, a broad-spectrum insecticide that belongs to the phenylpyrazole chemical family, induces massive and inhomogeneous changes in the serotoninergic systems in the rat brain [34]. Type II pyrethroids (with an α-cyano group) accelerated the turnover of serotonin in the midbrain and striatum areas of rats and so can affect serotonin neurotransmission levels [35].…”