Browsing by Author "Chaney, Shawnta Y."
Now showing 1 - 2 of 2
- Results Per Page
- Sort Options
Item Low-level human equivalent gestational lead exposure produces sex-specific motor and coordination abnormalities and late-onset obesity in year-old mice(Environmental Health Perspectives, 2008-03) Leasure, J. Leigh; Giddabasappa, Anand; Chaney, Shawnta Y.; Johnson, Jerry E., Jr.; Pothakos, Konstantinos; Lau, Yuen-Sum; Fox, Donald A.Background. Low-level developmental lead exposure is linked to cognitive and neurological disorders in children. However, the long-term effects of gestational lead exposure (GLE) have received little attention. Objectives. Our goals were to establish a murine model of human equivalent GLE and to determine dose–response effects on body weight, motor functions, and dopamine neurochemistry in year-old offspring. Methods. We exposed female C57BL/6 mice to water containing 0, 27 (low), 55 (moderate), or 109 ppm (high) of lead from 2 weeks prior to mating, throughout gestation, and until postnatal day 10 (PN10). Maternal and litter measures, blood lead concentrations ([BPb]), and body weights were obtained throughout the experiment. Locomotor behavior in the absence and presence of amphetamine, running wheel activity, rotarod test, and dopamine utilization were examined in year-old mice. Results. Peak [BPb] were < 1, ≤ 10, 24–27, and 33–42 μg/dL in control, low-, moderate- and high-dose GLE groups at PN0–10, respectively. Year-old male but not female GLE mice exhibited late-onset obesity. Similarly, we observed male-specific decreased spontaneous motor activity, increased amphetamine-induced motor activity, and decreased rotarod performance in year-old GLE mice. Levels of dopamine and its major metabolite were altered in year-old male mice, although only forebrain utilization increased. GLE-induced alterations were consistently larger in low-dose GLE mice. Conclusions. Our novel results show that GLE produced permanent male-specific deficits. The nonmonotonic dose-dependent responses showed that low-level GLE produced the most adverse effects. These data reinforce the idea that lifetime measures of dose–response toxicant exposure should be a component of the neurotoxic risk assessment process.Item Retinal development and age related degeneration following gestational lead exposure(2013-08) Chaney, Shawnta Y.; Fox, Donald A.; Eichberg, Joseph; Johnson, Jerry E., Jr.; Gunaratne, Preethi H.PURPOSE: Gestational lead exposure (GLE) increased and prolonged retinal progenitor cell proliferation in mice, resulting in a dose-dependent increase in two late-born retinal neurons: rod photoreceptors and bipolar cells. The present goals were to examine: 1) the spatiotemporal differentiation and functional development of these two cell types, 2) the profile of glutamatergic responses in developing retina prior to canonical synaptic function, and 3) the structural integrity of aging retinas after GLE. METHODS: RT-qPCR, immunohistochemistry, confocal microscopy, agmatine probe labeling, and pharmacological assays. RESULTS: GLE decreased the relative expression of rod specific genes at PN2; delayed the differentiation and functional development of rod photoreceptors and bipolar cells by 2-3 days; increased and prolonged the glutamatergic response of post-mitotic rod and bipolar precursors in the ventricular zone of developing retina; and increased and accelerated the age-related degeneration of rod photoreceptors and bipolar cells. CONCLUSIONS: Gestational exposure to environmental toxicants such as lead can produce differential age-dependent effects on the developing and aging retina. Furthermore, the lifespan effect of increased proliferation can result in degeneration later in life.