Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


10513.pdf (1.84 MB)

ETD Abstract Container

Abstract Header

Developmental neurotoxicity of manganese: behavioral and cognitive deficits in the context of a complex environment

Amos-Kroohs, Robyn M
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406901642

Abstract Details

2014, PhD, University of Cincinnati, Medicine: Molecular and Developmental Biology.
Manganese (Mn) is an essential metal, but a neurotoxin when in excess of bodily requirements. The neurotoxic properties of Mn were first seen in adults following occupational inhalation exposure. Mn is associated with a Parkinson’s like disorder consisting of behavioral changes, neurological deficits, and motor deficits that include dystonia and bradykinesia. In children Mn overexposure (MnOE) is associated with cognitive deficits, behavioral disinhibition, decreased IQ, and decreased performance on school-related tasks. The neurotoxic effects of MnOE in children are increased due to an underdeveloped gastrointestinal system and the developing nervous system is vulnerable to toxins. Toxins, such as MnOE, do not occur in isolation. Toxin effects are likely modified by series of environmental elements that are risk factors for decreased developmental potential in children. Two of these, iron deficiency (FeD) and developmental stress (DS), cause detrimental effects in children and modify the harmful effects of neurotoxic metal exposure. Subclinical FeD affects up to 15% of US children and exacerbates Mn toxicity due to increased Mn bioavailability. FeD is prevalent in impoverished and low socioeconomic environments and these conditions induce DS. MnOE, FeD, and DS are combined here to model a `real world’ exposure scenario. Pregnant rats and their litters were housed in cages with a wire grid floor or standard bedding from embryonic day (E)7 to postnatal day (P)28. Dams were fed a 90% FeD or standard NIH-07 diet from E15 through P28. Within each litter, different offspring were treated with 100 mg/kg Mn (100Mn) by oral gavage or vehicle (VEH) every other day from P4 to P28. All treatments ended at weaning (P28). We posited that the combination of these factors would disrupt both DA and 5HT neurotransmitters systems, creating behavioral and cognitive deficits that were exacerbated under the combination of conditions as opposed to solely MnOE. We first investigated the combination of MnOE and FeD, verifying our FeD model and examining their combined effects on several neurotransmitter systems. We then added DS, the BAR cage, and conducted a behavioral phenotype of the animals, including behavioral assays at two different ages and cognitive assays as adults. Finally, we investigated potential molecular and mechanistic endpoints in an effort to determine how MnOE, FeD, and BAR cage, as well as the combination, might affect behavior and cognition in these rats. We found that MnOE causes spatial and non-spatial learning deficits, as well as decreases in social and sucrose preference. We also found concurrent increases in DA and DOPAC, but serotonergic systems appeared to be unaffected by MnOE. Posited interactions between MnOE, FeD diet, and BAR cage were minimal and transient, but present. DS also caused cognitive and behavioral changes. These findings implicate DAergic dysfunction in behavioral and cognitive deficits heretofore not found in a rodent model.
Michael Williams, Ph.D. (Committee Chair)
Erin Haynes, Dr.P.H. (Committee Member)
Kenneth Campbell, Ph.D. (Committee Member)
Steve Danzer, Ph.D. (Committee Member)
Mary Beth Genter, Ph.D. (Committee Member)
Charles Vorhees, Ph.D. (Committee Member)
200 p.
Toxicology
Manganese; Iron Deficiency; Developmental Stress; Neurotoxicology; Cognition

Recommended Citations

Citations

  • Amos-Kroohs, R. M. (2014). Developmental neurotoxicity of manganese: behavioral and cognitive deficits in the context of a complex environment [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406901642

    APA Style (7th edition)

  • Amos-Kroohs, Robyn. Developmental neurotoxicity of manganese: behavioral and cognitive deficits in the context of a complex environment. 2014. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406901642.

    MLA Style (8th edition)

  • Amos-Kroohs, Robyn. "Developmental neurotoxicity of manganese: behavioral and cognitive deficits in the context of a complex environment." Doctoral dissertation, University of Cincinnati, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406901642

    Chicago Manual of Style (17th edition)

ucin1406901642
464
© 2014, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.