Developmental Exposure to Atrazine Impairs Spatial Memory and Downregulates the Hippocampal D1 Dopamine Receptor and cAMP-Dependent Signaling Pathway in Rats

Abstract

Atrazine (ATR) is a widely used herbicide that has been implicated as a neurotoxicant. Recent experimental evidence has implicated that ATR exposure also appears to have adverse effects on the hippocampus, which is a critical region for learning and memory. The aim of the present study was to investigate the effects of ATR toxicity on the hippocampus of developing rats. Postnatal day (PND) 28 male Sprague–Dawley (SD) rats received ATR by oral gavage at 10 or 100 mg/kg bodyweight (BW) for 30 consecutive days and were sacrificed at PND 90. Behavioral test results indicated that spatial learning and memory were affected by ATR treatment. Electron microscopy analysis showed that the ultrastructures of the hippocampus were altered in the ATR-treated groups, as compared to the control group. Additionally, ATR treatment impacted dopamine and D1 dopamine receptor (D1DR) contents through different mechanisms. Reduced mRNA and protein expression levels of factors involved in the cAMP-dependent signaling pathway were also detected. These results indicate that the developmental exposure of rats to ATR can damage the hippocampus and spatial memory, which might be related to the downregulation of expression levels of the D1DR and its downstream signaling pathway.

Paternal exposure to a common herbicide alters the behavior and serotonergic system of zebrafish offspring

“…The mechanism underlying atrazine neuroendocrine disruption still remains to be resolved, but is implicated in disrupting a variety of pathways including the hypothalamicpituitary gonadal axis [56][57][58][59], monoaminergic systems within the central nervous system [5,54,[60][61][62], alterations to the cyclic adenosine monophosphate (cAMP) dependent signaling pathway [63][64][65][66][67], as well as many epigenetic mechanisms, including microRNAs and expression of DNA methyltransferases (see [55] for more details; [7,68]). Previous research has demonstrated that atrazine exposure in fish can reduce mating behavior (male-male aggression in a courtship context; [3,68]) and alter some aspects of sociability [69], personality phenotypes in crayfish [70], increased anxiety and reduced spatial memory and learning in rodents [54, 67,71], but to our knowledge, no study has yet explored how atrazine may affect behavioral traits of unexposed offspring. We hypothesized that if changes in progeny behavior (relative to controls) occurred, this would provide evidence that the herbicide atrazine has the capacity to influence behavior across generations, and these changes are likely to be attributed to a non-genetic, paternal component of inheritance.…”

Hypoactivity, Abnormal Musculature, and Learning and Memory Defects in slc6a3 zebrafish Mutant Larvae

“…In mammals, DA regulates hippocampaldependent learning. In previous mouse slc6a3 mutants, it was reported that the decrease in slc6a3 expression in mice impaired learning in a running experiment [39] . In patients with Parkinson's disease, the expression level of slc6a3 is signi cantly reduced and is accompanied by learning and memory impairments [40] .…”

Atrazine Inhalation Causes Neuroinflammation, Apoptosis and Accelerating Brain Aging

“…Additionally, the mice were weighted and observed for any clinical symptoms, and the information was recorded by the animal care staff. At the end of experiment, the mice were sacrificed by cervical dislocation under anesthesia and brain were collected for different analysis, as previously described [ 37 , 38 , 65 , 68 , 69 , 70 ]. The ATR dosage was chosen based on other previous studies, but for the first time, ATR was not administered by oral gavage but instead by aerosol, because there is still limited knowledge of the effects of ATR on the brain [ 45 , 58 , 71 ] ( Figure S1 ).…”