Maternal malnutrition, infection, stress, and even mutations can perturb the gestational environment, resulting in increased risk for offspring to develop behavioral abnormalities in both human and animal models. We reported the gestational effect of the inactivation of the maternal 5-HT1A receptor (R) in mice, manifested as anxiety and increased stress responsiveness in the offspring. The consequences of these maternal conditions are often not limited to the first generation, and have actually been found to alter the behavior of the grandchildren. Our recent data show that the anxiety-inducing effect of maternal 5-HT1AR deficit is extended to the F2 generation (grandchildren). Although such intergenerational non-genetic "inheritance" of behavior increases the incidence of neuropsychiatric disease in the population, the underlying mechanism by which this occurs is essentially unknown. Using embryo transfer and whole genome epigenetic analysis, we study how the behavioral and epigenetic effects of adverse gestational environment propagate to two consecutive generations of offspring.

Public Health Relevance

Maternal malnutrition, infection, stress, and mutations can significantly perturb the gestational environment, resulting in increased risk for developing behavioral abnormalities in children and even grandchildren. Although such intergenerational non-genetic inheritance of behavior increases the incidence of neuropsychiatric disease in the population, the underlying mechanism by which this occurs is essentially unknown. Here we propose a study to specify the cellular and epigenetic mechanism underlying such grandmother effect in an animal model.

Agency
National Institute of Health (NIH)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21MH103715-01
Application #
8681843
Study Section
Molecular Neurogenetics Study Section (MNG)
Program Officer
Beckel-Mitchener, Andrea C
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10065