Abstract
Limbic system associated membrane protein (Lsamp) gene is involved in behavioral adaptation in social and anxiogenic environments and has been associated with a broad spectrum of psychiatric diseases. Here we studied the activity of alternative promoters of Lsamp gene in mice in three rearing conditions (standard housing, environmental enrichment and social isolation) and in two different genetic backgrounds (129S6/SvEv and C57BL/6). Isolation had no effect on the expression levels of Lsamp. Environmental enrichment elevated the expression levels of Lsamp 1b transcript specifically in the hippocampus in B6 mice, and the same tendency existed across both mouse lines and both transcripts. Furthermore, we showed that the density of cells exhibiting 1b promoter activity is remarkably higher in the subgranular zone of the dentate gyrus in the hippocampal formation which is a specific area of enrichment-induced neurogenesis in adult rodents. On the contrary to 1b, 1a promoter is selectively active in the pyramidal and granule cell layers. We provide evidence that Lsamp modulates enrichment-induced activation of Bdnf as the enrichment-induced elevation of Bdnf in the hippocampus is significantly diminished in Lsamp-deficient mice; furthermore, a significant correlation was found between the expression levels of Lsamp and Bdnf transcripts in the hippocampus and frontal cortex. Significant strain differences in Lsamp expression were detected in the hippocampus, frontal cortex and thalamus that could be related to the different behavioral phenotype of B6 and 129Sv mice. Our data provides further evidence that LSAMP is implicated in the hippocampal connectivity and plasticity thereby modulating adaptability in changing environments.
Highlights
A growing field of social genomics research has begun to identify the specific types of genes that are subject to socialenvironmental regulation, the neural, and molecular mechanisms that mediate the effects social processes have on gene expression (Slavich and Cole, 2013)
The trend of enrichment-induced elevation of both 1a and 1b transcripts exists in 129Sv and B6 background but is only statistically significant in the case of 1b promoter in B6 mice [Figure 1A, F(2, 42) = 3.98; p < 0.05]; in pooled backgrounds the effect is again significant in the case of 1b [Limbic system associated membrane protein (Lsamp) 1a F(2, 45) = 0.83, p = 0.44; Lsamp 1b F(2, 45) = 3.82 p < 0.05].There were no other enrichment- or isolation-induced effects on Lsamp expression
Lsamp 1a transcript was higher in the hippocampal area of 129Sv mice [Figure 1A; F(1, 46) = 6.92, p < 0.05] while Lsamp 1b had higher expression levels in the frontal cortex [Figure 1B; F(1, 46) = 4.92 p < 0.05] and thalamus [Figure 1E; F(1, 46) = 10.05 p < 0.01] of B6 mice
Summary
A growing field of social genomics research has begun to identify the specific types of genes that are subject to socialenvironmental regulation, the neural, and molecular mechanisms that mediate the effects social processes have on gene expression (Slavich and Cole, 2013). Enrichment and social isolation are the most common environmental manipulations used in laboratory rodent housing. It is vital to understand the molecular and functional impact of these environmental manipulations on the brain and behavior. Social isolation and rejection can influence the activity of a broad set of genes (Bibancos et al, 2007; Sestito et al, 2011) and cause permanent changes in the brain and behavior throughout lifespan (Fone and Porkess, 2008). The discovery that socialenvironmental factors can substantially alter the expression of meaningfully identified gene profiles represents a paradigm shift in thinking about gene-environment interactions (Slavich and Cole, 2013)
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