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Sex Differences in Mouse Hippocampal Astrocytes after In-Vitro Ischemia
Published on: October 25, 2016
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Mouse Strain and Sex-Dependent Differences in Long-term Behavioral Abnormalities and Neuropathologies after
Abigail Snyder-Keller1,2, Laura D Kramer3,2, Steven Zink3
1Wadsworth Center, New York State Department of Health, Albany, New York 12201, and Abigail.snyder-keller@health.ny.gov.
Summary
Neonatal Zika virus (ZIKV) exposure causes long-term behavioral issues like hyperactivity and motor deficits in mice. Susceptibility and outcomes vary by genetic strain and sex, with calcifications observed in affected brains.
Area of Science:
- Neuroscience
- Virology
- Developmental Biology
Background:
- Zika virus (ZIKV) exposure during development can lead to congenital Zika syndrome, including brain abnormalities.
- Neuropathologies like intracranial calcifications can occur even without microcephaly.
- The full spectrum of neurodevelopmental and behavioral impacts of ZIKV exposure is not fully understood.
Purpose of the Study:
- To investigate the long-term neurobehavioral consequences of neonatal ZIKV exposure in different mouse strains.
- To identify strain- and sex-dependent differences in ZIKV-induced neuropathology and behavior.
- To establish a foundation for understanding genetic and immune factors influencing ZIKV neurodevelopmental outcomes.
Main Methods:
- Neonatal infection of four inbred mouse strains (C57BL/6J, 129S1/SvImJ, FVB/NJ, DBA/2J) with ZIKV on postnatal day 1.
- Assessment of early viral susceptibility and glial responses in the brain.
- Long-term evaluation of behavioral abnormalities (hyperactivity, impulsivity, motor coordination) in adult mice.
- Histopathological examination for intracranial calcifications.
Main Results:
- Significant strain differences were observed in early ZIKV susceptibility and the timing of glial reactions.
- Neonatal ZIKV exposure resulted in long-lasting, strain- and sex-dependent behavioral deficits, including hyperactivity, impulsivity, and motor incoordination.
- Susceptible adult mice displayed widespread intracranial calcifications, potentially linked to observed behavioral deficits.
Conclusions:
- Developmental ZIKV exposure can induce significant and lasting neurobehavioral abnormalities in a mouse model.
- Genetic background and sex critically influence susceptibility to ZIKV neuropathology and subsequent behavioral outcomes.
- This study provides a framework for identifying factors that contribute to long-term neurodevelopmental consequences of early-life ZIKV infection.
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