Citation:

Oshiro, W., T. Beasley, K. McDaniel, V. Moser, AND D. Herr. Manganese consumption and perinatal stress cause persistent, sex-dependent, and complex changes in attentional function in rats. Presented at Developmental Neurotoxicology Society, Charleston, South Carolina, June 27 - July 01, 2020. https://doi.org/10.1016/j.ntt.2020.106885

Impact/Purpose:

Meeting Cancelled due to COVID-19 Global Pandemic. Abstracts were published in special issue of Journal for Neurotoxicol Teratol. 2020 May-June; 79: 106885  DNTS10  10.1016/j.ntt.2020.106885. Published online 2020 Apr 13. doi: 10.1016/j.ntt.2020.106885  PMCID: PMC7252070  PMID: 32298771  Background: The developmental effects of chemicals that co-occur in vulnerable populations with elevated physical and psychological stress is of increasing concern to risk assessors. Relevance: This research was conducted under Sustainable Healthy Communities task (SHC) 2.6.3 and addresses the interactions between chemical stressors and social factors that impact health and development. Manganese (Mn) overexposure can occur through drinking water and is a neurodevelopmental toxicant which has been associated with multiple adverse outcomes including cognitive impairment and attentional disorders. Stress during pregnancy may also alter neurodevelopment. In order to assess causality of these factors we developed a rodent model of co-occurring perinatal manipulations and conducted a series of behavioral assessments in male and female offspring. Study Description: Manganese was delivered in drinking water (0, 2, or 4 mg/ml Mn) of pregnant rats from gestational day (GD) 7 to postnatal day (PND) 22. A variable perinatal stress (PS) paradigm was applied to half of the animals from GD13 to PND9. Acoustic startle responses (ASR) and choice reaction time (CRT) were evaluated in adults. Observations: The ASR and its habituation were unaffected by stress or Mn, whereas prepulse inhibition of the ASR yielded a significant interaction of Mn, Stress, and prepulse noise; contrasts were not significant. Mn reduced accuracy in males performing a cued, but not uncued, CRT task and PS reduced accuracy in 0 mg/ml Mn males compared to NS-0 mg/ml males. PS increased female movement time (MT) but not decision time on both CRT tasks. A significant interaction of PS and Mn occurred on cued MT at the 4 mg/ml dose in both sexes. Impact: These data demonstrate the ability of both stress and Mn exposure during the perinatal period of development in the rat to impair attentional function and movement times later in adulthood. Furthermore, the data show evidence of perinatal stress modifying the effect of Mn on movement in both males and females.

Description:

DNTS P10 Manganese consumption and perinatal stress cause persistent, sex-dependent, and complex changes on attentional function in rats Wendy Oshiro 1, Tracey Beasley1, Kathy McDaniel1, Ginger Moser 2, David Herr1 1 US EPA, Research Triangle Park, USA. 2 Retired, US EPA, Research Triangle Park, USA Abstract The developmental effects of chemicals that co-occur in vulnerable populations with elevated physical and psychological stress are of increasing concern to risk assessors. In order to assess causality of these factors we developed a rodent model of co-occurring perinatal manipulations and conducted a series of behavioral assessments in male and female offspring. Manganese (Mn), a potential neurodevelopmental toxicant, was delivered in drinking water (0, 2, or 4 mg/ml Mn) of pregnant rats from gestational day (GD) 7 to postnatal day (PND) 22. A variable perinatal stress paradigm (PS) was applied to half of the animals from GD13 to PND9. Acoustic startle response (ASR) and choice reaction time (CRT) were evaluated in adults. The ASR and its habituation were unaffected by stress or Mn, whereas prepulse inhibition of the ASR yielded a significant interaction of Mn, Stress, and prepulse noise; however, contrasts were not significant. Mn reduced cued but not uncued CRT accuracy in males, and PS alone reduced accuracy in 0 mg/ml Mn-males compared to non-stress males. PS increased female movement time (MT) but not decision time on both CRT tasks. A significant interaction of PS and Mn occurred on cued MT at the 4 mg/ml dose in both sexes. These data demonstrate the ability of both PS and Mn to impair attentional function in adult animals. Furthermore, the data show evidence of PS modifying the effect of Mn on movement in both sexes. This abstract does not reflect EPA policy.  

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