Hypomethylation in the Hippocampus: Can Age-Related Cognitive Decline in Mice Be Reversed by the Activity of One Gene?

Partial ribbon structure of DNMT3a Source: Protein Database
Buried in the middle of the August issue of Nature Neuroscience is an article (1) by Oliveira, Hemstedt and Bading that caught my eye. It isn’t often that I see a paper about gene rescue in a neuroscience journal, especially in a study about cognitive decline.

I looked for a News and Views summary of the article, thinking that if the conclusions of the article were anything like what the title and abstract indicated, there must be an editorial summary. I wasn’t disappointed. Su and Tsai provided a nice summary of the paper and discussed some of the potential implications of the work (2). Continue reading “Hypomethylation in the Hippocampus: Can Age-Related Cognitive Decline in Mice Be Reversed by the Activity of One Gene?”

Remembering Not to Forget

Forgetting. Forgetting your address; your spouse; your children; your friends; your life. It is something that none of us want to think about, but it hangs over some of us like a specter. Can’t remember if you fed the cat? Where you put your car keys? Did you forget to pack your lunch or return a phone call? Maybe you are trying to do too many things at once, or maybe you are tired. There are lots of perfectly normal reasons why we all forget things from time to time, but every time I forget something there is a nagging voice in my head saying, “Maybe it is something else.” Continue reading “Remembering Not to Forget”

This is Your Hippocampus on Cortisol

A maze photo.
Whether navigating a maze or other obstacles, decreasing stress will help.

Research published by  Dr. Joyce Yau et al. in the Journal of Neuroscience earlier this year examined whether negative effects of cortisol on memory could be blocked using antagonists for brain receptors for cortisol.

The researchers noted that  local brain amplification of glucocorticoids (cortisol)  by 11beta-hydroxysteriod dehydrogenase type 1 (11beta-HSD1) is “pivotal” in age-related memory loss.

Cortisol acts by binding to cell receptors. In their research, Yau and colleagues found that when levels of cortisol are low, a particular cortisol receptor is bound. However, at higher concentrations, cortisol has a spillover effect and binds a second receptor. Binding to this second receptor activates cellular processes in the brain that cause memory impairment.

The  receptors studied were the high-affinity mineralocorticoid receptor (MR) and low-affinity glucocorticoid receptor (GR). As models for memory impairment, they used aged C57BL/6J mice as controls. Also studied were 11beta-HSD1-deficient mice (-/-), which ordinarily show no age-related memory deficits. Mouse memory was tested with a spatial memory task, a Y maze. Continue reading “This is Your Hippocampus on Cortisol”