Date of Degree

6-2021

Document Type

Thesis

Degree Name

M.S.

Program

Cognitive Neuroscience

Advisor

Yoko Nomura

Subject Categories

Behavioral Neurobiology | Developmental Neuroscience | Disability Studies | Genetics

Keywords

MeCP2, FOXP1, Intellectual Disability, Developmental Delay, Placenta, Epigenesis

Abstract

The complex interaction between gene expressions and environmental factors plays a key role in the pathogenesis of various diseases, including neurodevelopmental disorders (Lenroot & Giedd, 2008). This study aimed to evaluate first, the magnitude of association between placental gene Methyl-CpG Binding Protein 2 (MeCP2) and intellectual disability (ID) in the offspring and second, the synergy between placental gene Forkhead box protein 1(FOXP1) and developmental delay (DD) in the offspring. We focused on assessing two specific paradigms, i) placental gene expressions of MeCP2 among children that have ID vs. children without ID; and ii) placental gene expression of FOXP1 among children that have DD vs. children without DD. We measured the presence and severity of ID using Full Scale Intelligence Quotient (FSIQ) derived from the Wechsler Preschool & Primary Scale of Intelligence IV (WPPSI-IV) as well as the presence and severity of DD using a composite score from Bayley Scales of Infant Development (Bayley-III) and examined gene expressions of MeCP2 and FOXP1 in the placenta. Previous studies found concrete evidence that both MeCP2 and FOXP1 are implicated with neurodevelopmental disorders such as ID and DD (Chahrour et al., 2008; Meerschaut et al., 2017). We proposed to test whether hyper expressions of those two genes (MeCP2 and FOXP1) in placenta will be associated with children that have higher intellectual and developmental scores. We further examined the influence of prenatal stress, as measured by exposure to Hurricane Sandy, on the relationship between the placental expression of the two genes, and neurodevelopmental disorders ID and DD. A linear regression model demonstrated that there is a significant moderately positive correlation between MeCP2 gene expression and FSIQ score for children with ID. In contrast, we found that hyper-expression of the FOXP1 gene was associated with lower scores on the three domains of DD: motor development, language development and general adaptive development areas. In addition, the magnitude of the association between FOXP1 and DD in areas of language and general adaptive development was different in relation to exposure to Hurricane Sandy among mothers during pregnancy. Children whose mothers were exposed to Hurricane Sandy on average had a hyper-FOXP1 expression along with lower DD score. This suggests that prenatal stress further aggravates the magnitude of the association between FOXP1 and DD. These results demonstrate the intricate roles of genes (MECP2 and FOXP1) and environment (Hurricane Sandy) on neurodevelopmental disorders (ID and DD). To further advance our understanding of MECP2, FOXP1, ID and DD, more studies should be conducted to examine the impact of specific mutations in placental genes such as MECP2 & FOXP1 on ID and DD respectively, in offspring.

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