Zuloaga D G, Lahvis G P, Mills B, Pearce H L, Turner J, Raber J
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, United States.
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, United States.
Neurotoxicology. 2016 Mar;53:132-140. doi: 10.1016/j.neuro.2016.01.007. Epub 2016 Jan 18.
Domoic acid (DA) is an algal neurotoxin that accumulates in marine fish and shellfish. DA can move across the placenta and concentrate in amniotic fluid, which can be swallowed during late gestation. DA also transfers to infants via milk. Preclinical studies to determine effects of developmental DA expose have primarily involved DA exposure during the postnatal period and little is known about late CNS effects following prenatal DA. In the present study, we tested the hypothesis that prenatal exposure of FVB mice to low levels of DA would result in diminished social interaction and sensory motor gating associated with alterations in parvalbumin immunoreactivity in relevant brain regions undergoing development during and following DA exposure. In addition to parvalbumin, we stained with NeuN for a neuronal specific nuclear protein to determine if neuronal loss followed prenatal DA exposure. A single moderate dose of DA administered during gestation produces diminishes social investigation and alters sensorimotor gating, behavioral effects more pronounced in males than females. These behavioral changes were associated with discrete alterations in the parvalbumin-positive subtype of GABAergic neurons in the dentate gyrus and lateral amygdala.
软骨藻酸(DA)是一种藻类神经毒素,会在海鱼和贝类中蓄积。DA可穿过胎盘并在羊水中浓缩,在妊娠晚期可能会被胎儿吞咽。DA还会通过乳汁传递给婴儿。确定发育性DA暴露影响的临床前研究主要涉及出生后DA暴露,而对于产前DA暴露后中枢神经系统的后期影响知之甚少。在本研究中,我们检验了以下假设:产前将FVB小鼠暴露于低水平的DA会导致社交互动减少和感觉运动门控减弱,这与DA暴露期间及之后正在发育的相关脑区中小清蛋白免疫反应性的改变有关。除了小清蛋白,我们还用NeuN对神经元特异性核蛋白进行染色,以确定产前DA暴露后是否会出现神经元丢失。妊娠期单次给予中等剂量的DA会减少社交探究并改变感觉运动门控,行为影响在雄性中比雌性更明显。这些行为变化与齿状回和外侧杏仁核中GABA能神经元的小清蛋白阳性亚型的离散改变有关。