Altering Cell-Cell Interaction in Prenatal Alcohol Exposure Models: Insight on Cell-Adhesion Molecules During Brain Development

Abstract

Alcohol exposure during pregnancy disrupts the development of the brain and produces long lasting behavioral and cognitive impairments collectively known as Fetal Alcohol Spectrum Disorders (FASDs). FASDs are characterized by alterations in learning, working memory, social behavior and executive function. A large body of literature using preclinical prenatal alcohol exposure models reports alcohol-induced changes in architecture and activity in specific brain regions affecting cognition. While multiple putative mechanisms of alcohol’s long-lasting effects on morphology and behavior have been investigated, an area that has received less attention is the effect of alcohol on cell adhesion molecules (CAMs). The embryo/fetal development represents a crucial period for Central Nervous System (CNS) development during which the cell-cell interaction plays an important role. CAMs play a critical role in neuronal migration and differentiation, synaptic organization and function which may be disrupted by alcohol. In this review, we summarize the physiological structure and role of CAMs involved in brain development, review the current literature on prenatal alcohol exposure effects on CAM function in different experimental models and pinpoint areas needed for future study to better understand how CAMs may mediate the morphological, sensory and behavioral outcomes in FASDs.

Prenatal alcohol exposure alters expression of genes involved in cell adhesion, immune response, and toxin metabolism in adolescent rat hippocampus

“…In all of these, multiple categories were identified through differing analyses, strengthening their association in this study. The further validation of cell adhesion as responding to PAE once more serves to validate our study [46]. Our work supports these conclusions and furthermore indicates that they persist long after initial alcohol exposure, continuing into adolescence.…”

“…This is complemented by other cell adhesion genes that are upregulated in response to ethanol exposure, such as TCAM1 . The identification of cell adhesion in particular serves to validate our study, as previous work has demonstrated that PAE can alter cell-cell interactions through changes in cadherin expression during development [ 46 ]. Changes in expression of these genes suggest that prenatal ethanol exposure may lead to changes in neuronal connectivity that persist well past fetal development into adolescence.…”

“…However, we did not directly observe a change in expression of NCAM or L1. Instead, there was a significant downregulation of several protocadherins, another important class of cell adhesion molecules with known roles in cell-cell interactions [ 54 ] and previously shown to be altered by developmental alcohol exposure [ 46 ]. For example, in humans with FASD, there is an increase in DNA methylation of genes related to protocadherins in buccal samples [ 23 , 55 ].…”

Clinical Diagnosis and Management of Fetal Alcohol Spectrum Disorder and Sensory Processing Disorder in Children

“…Furthermore, alcohol can also influence the kinases that influence the CAMs functions [13]. These CAM-mediated activities are vital for the growth of the embryo, fetus, and newborn, resulting in developmental and behavioral abnormalities after birth, and could play a role in the development of FASD [11,14].…”

“…Physical development may be impacted by prenatal alcohol exposure, and postnatal adversity resulting in a growth impairment in height, weight, and head circumference. A growth deficiency is commonly identified when age-gender height and weight fall below the tenth percentile [14]. Growth delays increase a child's overall health risks by affecting their general health and cognitive and physical development.…”