Prenatal sodium arsenite affects early development of serotonergic neurons in the fetal rat brain

Abstract

Prenatal arsenite exposure has been associated with developmental disorders in children, including reduced IQ and language abnormalities. Animal experiments have also shown that exposure to arsenite during development induced developmental neurotoxicity after birth. However, the evidence is not enough, and the mechanism is poorly understood, especially on the exposure during early brain development. This study assessed effects of sodium (meta) arsenite shortly after exposure on early developing fetal rat brains. Pregnant rats were administered 50 mg/L arsenite in their drinking water or 20 mg/kg arsenite orally using a gastric tube, on gestational days (GD) 9-15. Fetal brains were examined on GD16. Pregnant rats administered 20 mg/kg arsenite showed reductions in maternal body weight gain and food consumption during treatment, but not with 50 mg/L arsenite. Arsenite did not affect fetal development, as determined by body weight, mortality and brain size. Arsenite also did not induce excessive cell death or affect neural cell division in any region of the fetal neuroepithelium. Thyrosine hydroxylase immunohistochemistry revealed no difference in the distribution of catecholaminergic neurons between fetuses of arsenite treated and control rats. However, reductions in the number of serotonin positive cells in the fetal median and dorsal raphe nuclei were observed following maternal treatment with 20mg/kg arsenite. Image analysis showed that the serotonin positive areas decreased in all fetal mid- and hind-brain areas without altering distribution patterns. Maternal stress induced by arsenite toxicity did not alter fetal development. These results suggest that arsenite-induced neurodevelopmental toxicity involves defects in the early development of the serotonin nervous system.

Effect of methotrexate exposure at late gestation on development of telencephalon in rat fetal brain

“…with MTX (30 mg/kg body weight) or saline (the control) on GD 16. The specific timing of MTX administration was selected, because GD 16 is the period when neuronal progenitor cells proliferated in VZ/SVZ and then move from VZ/SVZ to the side of meninges to form the subplate and cortical plate [ 37 , 44 ]. In our preliminary study, although MTX 5 and 15 mg/kg treatment on GD 16 induced few histopathological changes in the VZ/SVZ of the telencephalic wall and striatum in fetal brain, MTX 30 mg/kg treatment on GD 16 induced pyknotic changes in the same regions of rat fetal brain.…”

“…The cortical plate neurons are generated in an inside-out gradient and produce a laminar structure [ 38 ]. On gestation day (GD) 16 in rats, neural progenitor cells proliferate in VZ/SVZ and pass through the intermediate zone, move to the side of meninges and formed the subplate and cortical plate [ 27 , 37 , 44 ]. MTX exposure on GD 13 in rats induced apoptosis and inhibited cell proliferation of neuroepithelial cells in the VZ of telencephalon [ 49 ].…”

Ecologically relevant arsenic exposure alters female mate preference and anxiety-like behavior in Betta splendens

“…The mechanisms by which arsenic could alter behavior are unclear, but both direct and indirect actions are possible. For example, arsenic-induced behavioral changes could be via direct action on neural function [12, 13], or changes could be induced by influencing other behaviors that result in a reduced expression of preference. For example, arsenic has been shown to increase anxiety-like behavior in mice as measured by open-field and elevated-maze tests [14], and anxiety has been associated with altered behavior in a variety of contexts, including reproduction [15].…”