Yet again, the MTA provides New Yorkers with a laundry list of service advisories for the weekend. How are you ever going to make it anywhere on time?

Let’s face it. Living in New York City, we are under an unusual amount of stress. Perhaps this is the reason scientists at Rockefeller University are investigating the molecular basis of stress.

Recently in PLoS ONE, findings from the laboratory of Bruce McEwen suggest that regulation of a specific hippocampal receptor may be linked to stress and depression.

The hippocampus is particularly susceptible chronic stress, mainly due to the high number of corticosteroid receptors in that region of the brain. Thus, McEwen’s group decided to look at a particular subset of hippocampal receptors, called kainite receptors, that have recently been linked to various mental disorders, including depression, schizophrenia, and bipolar disorder. The kainite gene family is made up of five members: GluR5, GluR6, GluR7, KA1, and KA2. However, the actual kainite receptor is composed of various mixtures of the subunits.

In rats that were subjected to chronic stress by continuous restrain over a 21-day period, researchers found that there was increased expression of the KA1 subunit in the CA3 and dentate gyrus regions of the dorsal hippocampus. Though this was result was promising, the researchers wanted to be sure that this effect was a result of increased corticosteroid activation. Thus, they went on to treat rats with various doses of corticosterone and assayed for KA1 activity in the CA3 and dentate gyrus. Surprisingly, KA1 activity was significantly increased in the dentate gyrus but not in the CA3. More importantly, the increase in KA1 expression was only seen when using low-dose corticosterone. The increase in KA1 expression was abolished with higher dosing.

This study demonstrates the intricacy of kainite receptor signaling in the hippocampus. In fact, the authors suggest that the seemingly unusual effect of high-dose corticosterone treatment is often seen when examining glucocorticoids in the brain. Additionally, chronic stress, like that caused by continuous restraint, will only moderately increase corticosterone levels in the brain, further demonstrating the effect of low-dose corticosterone on KA1 expression. But, all-in-all, these findings help us to understand the complex nature of depression and other mental disorders, and why these conditions often take a substantial amount of time to improve.

Richard G. Hunter, Rudy Bellani, Erik Bloss, Ana Costa, Katharine McCarthy, Bruce S. McEwen (2009). Regulation of Kainate Receptor Subunit mRNA by Stress and Corticosteroids in the Rat Hippocampus PLoS ONE, 4 (1) DOI: 10.1371/journal.pone.0004328