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Chunk #24 — RESULTS — Evidence for a role of SLC6A15 in stress vulnerability

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The neuronal transporter gene SLC6A15 confers risk to major depression.
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Epidemiological studies on MD report a 2–3 fold risk increase for individuals exposed to chronic stress (Wang, 2005) and twin studies clearly point to an increased susceptibility for MD as a result of a combination of environmental and genetic risk factors (Kendler et al., 2002). To further validate a role for SLC6A15 in MD, we used microarray gene-expression data from the hippocampus of mice subjected to chronic stress according to a recently developed and extensively validated mouse paradigm of chronic social stress in which susceptible animals show behavioural, endocrine as well as molecular changes reminiscent of a depression like phenotype (Schmidt et al., 2007; Schmidt et al., 2009) (fig. S5). We selected the 6 most susceptible and the 6 most resilient individuals from a formerly stressed group of 120 mice. Pooled mRNA samples of laser-assisted microdissections from the CA subregion 1 (CA1) of the hippocampus from both experimental groups (supplemental methods) were analysed on genome-wide Illumina BeadChips. Expression data for the probes specific for the genes in the associated region, TMTC2, SLC6A15, LRRIQ1 and ALX1 were compared between the two