Format

Send to

Choose Destination
Neurotoxicol Teratol. 2019 Jan 25;73:1-8. doi: 10.1016/j.ntt.2019.01.003. [Epub ahead of print]

Preclinical modeling of exposure to a global marine bio-contaminant: Effects of in utero Domoic acid exposure on neonatal behavior and infant memory.

Author information

1
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA; Washington National Primate Research Center, Seattle, WA, USA. Electronic address: ksg@uw.edu.
2
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA; Washington National Primate Research Center, Seattle, WA, USA.
3
Washington National Primate Research Center, Seattle, WA, USA.
4
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.
5
Department of Pharmaceutics, University of Washington, Seattle, WA, USA.
6
Center on Human Development and Disability, University of Washington, Seattle, WA, USA; Department of Pharmaceutics, University of Washington, Seattle, WA, USA.
7
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA; Center on Human Development and Disability, University of Washington, Seattle, WA, USA; Washington National Primate Research Center, Seattle, WA, USA.

Abstract

Domoic Acid (DA) is a naturally-occurring marine neurotoxin that is increasingly recognized as an important public health issue. Prenatal DA exposure occurs through the maternal consumption of contaminated shellfish/finfish. To better understand the fetal risks associated with DA, we initiated a longitudinal, preclinical study focused on the reproductive and developmental effects of chronic, low-dose oral DA exposure. To this end, 32 adult female Macaca fascicularis monkeys were orally dosed with 0, 0.075 or 0.15 mg/kg/day DA on a daily basis prior to breeding and throughout breeding and pregnancy. The doses included the proposed human Tolerable Daily Intake (TDI) (0.075 mg/kg/day) for DA. Adult females were bred to nonexposed males. To evaluate development during early infancy, offspring were administered a Neonatal Assessment modeled after the human Neonatal Behavior Assessment Scale and a series of Visual Recognition Memory problems using the novelty paradigm. Results indicated that prenatal DA exposure did not impact early survival reflexes or responsivity to the environment. Findings from the recognition memory assessment, given between 1 and 2 months of age, showed that exposed and control infants demonstrated robust novelty scores when test problems were relatively easy to solve. Performance was not diminished by the introduction of delay periods. However, when more difficult recognition problems were introduced, the looking behavior of the 0.15 mg/kg DA group was random and infants failed to show differential visual attention to novel test stimuli. This finding suggests subtle but significant impairment in recognition memory and demonstrates that chronic fetal exposure to DA may impact developing cognitive processes.

KEYWORDS:

Domoic acid; Infant; Macaque; Memory; Prenatal exposure

PMID:
30690118
DOI:
10.1016/j.ntt.2019.01.003

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center