Altered neurotransmission and neuroimaging biomarkers of chronic arsenic poisoning in wild muskrats (Ondatra zibethicus) and red squirrels (Tamiasciurus hudsonicus) breeding near the City of Yellowknife, Northwest Territories (Canada)

Chronic arsenic poisoning has been shown to be a risk factor for the development of intellectual disability. Numerous human and animal studies have also confirmed that low-level arsenic exposure has deleterious effects on neurotransmission and brain structures which have been further linked to neurobehavioral disorders. The aim of this present work was to comparatively assess structural brain volume changes and alteration of two (2) neurotransmitters, specifically dopamine (DA) and serotonin (5-HT) in the brains of wild muskrats and squirrels breeding in arsenic endemic areas, near the vicinity of the abandoned Giant mine site in Yellowknife and in reference locations between 52 and 105 km from the city of Yellowknife. The levels of DA and 5-HT were measured in the brain tissues, and Magnetic Resonance Imaging (MRI) was used to attempt brain volume measurements. The results revealed that the concentrations of DA and 5-HT were slightly increased in the brains of squirrels from the arsenic endemic areas compared to the reference site. Further, DA and 5-HT were slightly reduced in the brains of muskrats from the arsenic endemic areas compared to the reference location. In general, no statistically significant neurotransmission changes and differences were observed in the brain tissues of muskrats and squirrels from both arsenic endemic areas and non-endemic sites. Although MRI results showed that the brain volumes of squirrels and muskrats were not statistically different between sites after multiple comparison correction; it was noted that core brain regions were substantially affected in muskrats, in particular the hippocampal memory circuit, striatum and thalamus. Squirrel brains showed more extensive neuroanatomical changes, likely due to their relatively smaller body mass, with extensive shrinkage of the core brain structures, and the cortex, even after accounting for differences in overall brain size. The results of this present study constitute the first observation of neuroanatomical changes in wild small mammal species breeding in arsenic endemic areas of Canada.