Mood-related behavioral and neurochemical alterations in mice exposed to low chlorpyrifos levels during the brain growth spurt

Abstract

Organophosphates are among the most used pesticides. Particularly, chlorpyrifos (CPF) is responsible for a number of deleterious effects on brain development, which may program behavioral changes later in life. Here, we investigated whether a regimen of early low level CPF exposure that did not result in a significant inhibition of acetylcholinesterase (AChE) had deleterious effects on mood-related behaviors, as well as on cholinergic and serotonergic biomarkers in the mice brain. From the 3 rd to 9 th postnatal day (PN), male and female Swiss mice were subcutaneously injected with CPF. Mice were submitted to a battery of behavioral tests from PN60 to PN63: open field, elevated plus maze and forced swimming tests. The cholinergic and serotonergic biomarkers were assessed at PN10 and PN63. Our data indicated that early CPF exposure increased anxiety-like behavior in females and altered decision-making behavior in both sexes. Most biochemical alterations were sexdependent and restricted to females. At PN10, CPF female mice showed increased serotonin and choline transporter binding in cerebral cortex. Distinctively, in adult females, the effects indicated a hypoactive state: CPF exposure reduced 5-HT 1a receptor binding in cerebral cortex, as well as serotonin transporter binding and choline acetyltransferase activity in brainstem. Our results indicate that CPF exposure during the brain growth spurt deregulates serotonergic and cholinergic biomarkers. The effects are consistent with impaired synaptic function, may be related to long-term mood disorders and point out to higher female susceptibility.

Pesticide-Induced Alterations in Locomotor Activity, Anxiety, and Depression-like Behavior Are Mediated through Oxidative Stress-Related Autophagy: A Persistent Developmental Study in Mice

“…All of these findings indicate significant anxiety/depression-like behavior in pesticide-exposed F1 mice. These results are consistent with some studies of increased anxiety-like behaviors in mice, rats, and zebrafish exposed to CPF, 21 DDV, 80 and CP. 81 Epidemiological evidence suggests that CPF may affect the developing nervous system at low doses.…”

“…A good body of literature has demonstrated that the development of the brain is particularly susceptible to exposure to various pesticides (e.g., OPPs), even at doses below the threshold for systemic toxicity. 21 The disruptions in the developing nervous system have been associated with altered cognition, impaired motor control, and behavioral deficits in rodents. 79 In the current study, we found that the mice exposed to pesticides spent less time and traveled shorter distances in the center zone, with more feces in the OFT.…”

“…17−19 Additionally, recent studies revealed that OPPs can induce serotonergic system disturbances and mood disorders. 20,21 OPPs have high stability, and their half-life ranges from more than 2 days to several weeks. 22 Therefore, these pesticide residues remain in soil, food, and water and affect human health.…”

Protective effect of total saponins of ginseng stems and leaves (GSLS) on chlorpyrifos-induced brain toxicity in mice through the PTEN/PI3K/AKT axis

“…altered activity and impulsivity [7][8][9]. Up to the present, related studies have provided sufficient evidence to show that there exists a strong link between CPF exposure, long-term persistent cognitive impairment and increased risk of neurodegenerative diseases [10,11].…”

Adolescent intermittent ethanol exposure reduces astrocyte-synaptic proximity in the adult medial prefrontal cortex in rats: Reversal by gabapentin

“…However, due to the low power of interactions at a given sample size relative to main effects, interactions at p < 0.1 were examined as to whether lower-order effects were detectable after subdivision of the interactive variables [ 44 ]. This criterion for interactions was used to identify interactive factors requiring subdivision for lower-order tests of effects of AIE and gabapentin [ 1 , 4 , 6 , 17 , 36 ]. There is no widespread agreement in the field on controlling for the False Discovery Rate when making planned comparisons or its effects on Type I error.…”