The role of docosahexaenoic acid in stress reprogramming and behavior

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] The role of DHA (Docosahexaenoic acid [22:6(n-3)]) is known to play an important role in complex behaviors such as learning and memory, anxiety and depression. The work presented in this dissertation examines the role of DHA on sex-specific outcomes in two stress paradigms, social isolation in adulthood and chronic variable stress during pregnancy. In an animal model of early prenatal stress, reprogramming occured disproportionally in males, without an effect on females, and DHA enrichment provides a buffer against male-specific reprogramming in response to prenatal stress. Similarly, social isolation during adulthood results in sex-specific anxiety- and depressive-like phenotypes, which are reversed by DHA enrichment. males exhibited elevated anxiety-like behavior and anhedonia with parallel changes in gene expression patterns in the nucleus accumbens and ventral tegmental area, while DHA-enrichment reverses the male-specific anxiety-like behavior and anhedonia following social isolation and induces contrasting gene expression patterns in the nucleus accumbens and ventral tegmental area. Interestingly, DHAenrichment exhibited no disruptive or beneficial effect on females in either mouse model of stress, highlighting the possibility that the stress - diet axis exhibit separate mechanisms in males and females. These studies provide evidence that DHA enrichment during development, at least in part, regulates response to stress in a sex-specific manner by inducing sex-specific gene expression patterns that may lead the downstream expression of sex-specific behaviors.