Researchers from the University of Maryland have conducted a series of experiments in mice and humans leading them to conclude that reduced gene expression in the reward center is linked to depression. Specifically, the researchers found that there was reduced expression of the Slc6a15 gene in the brains of people with major depression who committed suicide, and that expression of this gene in the nucleus accumbens (reward center) in mice appeared to be tightly correlated with social defeat behavior which is one of the best animal models for depression.
The researchers had previously shown that expression of the Slc6a15 gene, which codes for a neutral amino acid transporter, was increased in the dopamine 2 neurons in the nucleus accumbens.
In these studies they showed that mice who were susceptible to chronic social defeat stress showed reduced expression of this gene. They also showed that gene expression was reduced in individuals with major depressive disorder. Finally, they showed that this reduction was localized to the dopamine 2 neurons in the nucleus accumbens. In fact it was specifically in a subtype of dopamine 2 neurons (medium spiny neurons) that the reduction occurred.
They speculate in their article about why this change may lead to depression but the answer is not clear right now.
Readers of this blog may recall an earlier post suggesting that increased expression of a different gene SIRT1 in dopamine 1 receptors in the nucleus accumbens was linked to depression and anxiety.
Obviously we are at the early stage in understanding how gene expression in this area of the brain may be linked to human depression.
Kim HD, Hesterman J, Call T, Magazu S, Keeley E, Armenta K, Kronman H, Neve RL, Nestler EJ, Ferguson D. SIRT1 Mediates Depression-Like Behaviors in the Nucleus Accumbens. J Neurosci. 2016 Aug 10;36(32):8441-52. doi: 10.1523/JNEUROSCI.0212-16.2016. PubMed PMID: 27511015; PubMed Central PMCID: PMC4978803.
Chandra R, Francis TC, Nam H, Riggs LM, Engeln M, Rudzinskas S, Konkalmatt P, Russo SJ, Turecki G, Iniguez SD, Lobo MK. Reduced Slc6a15 in Nucleus Accumbens D2-Neurons Underlies Stress Susceptibility. J Neurosci. 2017 Jul 5;37(27):6527-6538. doi: 10.1523/JNEUROSCI.3250-16.2017. Epub 2017 Jun 2. PubMed PMID: 28576941.
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