Zika virus (ZIKV) infection in pregnant women has been linked to a number of neurological disorders and complications in the offspring. Emerging evidence suggests that ZIKV preferentially infects neural progenitor cells resulting in the arrest of the neural progenitor cell cycle and ultimately the death of neural progenitor cells in the developing brain [3-5]. As a result, at its most extreme, prenatal ZIKV infection can result in severe neurological disorders including microcephaly; however, scientists have postulated that microcephaly may only be the ?tip of the iceberg? with regards to the neurological and cognitive consequences that may be associated with prenatal ZIKV infection. The purpose of the current proposal is to examine the long-term consequences of prenatal ZIKV infection using a novel rodent model. Dr. Schwarz's lab has recently found that infection of pregnant female rats with ZIKV significantly impacts the developing fetal brain of the offspring. Specifically, prenatal ZIKV infection increases cell death and reduces hippocampal and cortical volumes in the neonatal brain of the offspring. Moreover, prenatal ZIKV infection results in detectable levels of ZIKV in the neonatal serum at 7 days post infection and in the juvenile serum at 25 days post infection, suggesting that it may take weeks, if not longer, before the virus is fully cleared by the rat's immune system. The unique goal of these experiments is to (1) determine the location and duration of ZIKV in the brain following prenatal infection, (2) determine whether prenatal ZIKV infection results in long-term deficits in neurogenesis or the survival of these newborn neurons in the juvenile and adult brain, and (3) determine whether prenatal ZIKV infection results in later-life deficits in hippocampal dependent learning. The data obtained in these experiments, will allow scientists and clinicians to better understand the potential negative impact of prenatal ZIKV infection on later-life neurogenesis, an important neural process that is essential for cognitive function.

Public Health Relevance

Zika virus (ZIKV) infection in pregnant women has been linked to a number of neurological disorders and complications in the affected offspring. Emerging evidence suggests that ZIKV preferentially infects neural progenitor cells, resulting in the arrest of the neural progenitor cell cycle and ultimately the death of neural progenitor cells in the developing brain. The goals of these experiments is to determine (1) the location and duration of ZIKV in the brain after prenatal infection, (2) whether prenatal ZIKV infection results in long-term deficits in neurogenesis or the survival of new born neurons in the juvenile and adult brain, and (3) whether prenatal ZIKV infection results in later-life deficits in hippocampal-dependent learning.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HD096309-01A1
Application #
9824823
Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Chakhtoura, Nahida Abdo
Project Start
2019-08-15
Project End
2021-07-31
Budget Start
2019-08-15
Budget End
2020-07-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Delaware
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
059007500
City
Newark
State
DE
Country
United States
Zip Code
19716