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Browsing by Author "Urpa, Lea M."

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  • Urpa, Lea M. (2016)
    Anxiety disorders are the most frequently reported mental health disorder in Europe and treatment outcomes for approximately 30% of patients remains poor. Development of new therapies has been hindered by the fact that neural mechanisms of anxiety disorders are poorly understood. Anxiety is known to be heritable but genetic studies have failed to identify significant gene variants, and it appears that it may not be fully explained by common genetic variation. Recent work has suggested that this 'missing heritability' may in part be explained by epigenetic mechanisms, which include the regulation of transposable elements (TEs). Transposable elements are mobile genetic elements that possess the capability to move their location within a genome. TEs have been found to be specifically repressed in the rodent brain following stress, and also have been found to be overexpressed in human brain tissues and animal models of several neuropsychiatric disorders including schizophrenia and post-traumatic stress disorder. Given the evidence of transposable element overexpression in human patients and animal models of psychiatric disorders, we hypothesized that rodents who underwent psychosocial stress would have differential expression of TEs corresponding to their resilience or susceptibility to anxiety-like behaviors. In this study we examined the expression of transposable elements in C57BL/6Crl and DBA/2Crl inbred mouse strains following chronic social defeat stress. We also examined the baseline levels of six inbred strains (DBA/2J, A/J, 129S/SvImJ, C3H/HeJ, C57BL/6J, and FVB/NJ) that were previously characterized for innate anxiety levels. Overall expression of transposable elements was examined with RNA sequencing, while the expression of Long Interspered Element 1 (LINE-1) family TEs was evaluated with quantitative real-time PCR. We found that following psychosocial defeat, C57BL/6 and DBA/2 animals had strain-specific differences in transposable element expression in the ventral hippocampus but not the medial prefrontal cortex. In the ventral hippocampus, C57BL/6Crl animals resilient to anxiety-like behaviors appeared to have distinctly different transposable element expression profiles compared to control and resilient C57BL/6Crl animals. Conversely, DBA/2Crl animals susceptible to anxiety-like behaviors appeared to have distinctly different transposable element expression profiles from DBA/2Crl controls. We also observed innate strain differences between C57BL/6Crl and DBA/2Crl animals in both the medial prefrontal cortex and the ventral hippocampus and some differences between the six inbred strains in LINE-1 family TE expression. Our findings of differential transposable element expression in the hippocampus following psychosocial stress fits in with the current work on TE activity in the adult brain, which indicates that TE activity in the hippocampus may contribute to adult somatic neural diversity and plasticity. We suggest that a mechanistic effect of variable TE expression may exist that contributes to an individual's susceptibility or resilience to anxiety-like behaviors. Further work identifying de novo TE insertions at the genomic level needs to be done to identify the specific role that differential TE expression may be playing in the neural response to psychosocial stress.