Rockefeller UniversityWomen with premenstrual disorders are known to have frequent mood swings which could actually play havoc with their routine life. This latest research by experts from the Rockefeller University along with colleagues at Weill Cornell Medical College claims to have identified a gene that seems to have a likely role in premenstrual disorder. The gene, scientists explain could be a strong candidate for involvement in premenstrual dysphoric disorder (PMDD) and other maladies linked to natural flux in hormones during the menstrual cycle.

As per the researchers, detail experiments in mice appeared to have demonstrated the workings of a common variant of the particular gene. It was found to not only augment anxiety while dampening curiosity but also plucking the effects of estrogen on the brain which could impair memory. These findings if applied in the clinic could aid in the diagnosis and treatment of cognitive and mood disorders associated with menstrual cycle.

Researchers suggest it may also inform treatments in the course of menopause like hormone replacement therapy. The experiments were based in on the gene for a protein which among other activities was also found to work with estrogen. It could be doing so to enhance the adaptability of neurons in the hippocampus which is a brain region known to play a key role in mood, cognition and memory.

Apparently an alteration in one amino acid in this gene named brain-derived neurotrophic factor (BDNF), possibly creates the variant BDNF Met. The latter is supposedly carried by 20 to 30 percent of Caucasian women. Past research appears to have demonstrated that it could be a risk factor for psychiatric problems like depression and bipolar disorder. It may also be generally related with higher anxiety and impaired memory.

The scientists demonstrated that the performance of memory tasks by mice that possessed both the variant and the regular gene depended on their location in their estrous cycles. The finding is claimed to be the first instance that a genotype has been shown to communicate with a hormone cycle, such that it may influence a cognitive behavior. This was as per one reviewer of the paper.

In addition to this, the researchers also exhibited that mice that had the variant gene were more skittish. This implied that they probably spent much less time in the vulnerable center of a well-lit cage before scurrying to a corner. This resulted in them spending less time exploring objects that were placed in their cage.

“Even though the BDNF Met mice spent less time exploring these objects, they still showed the basic curiosity that all mice show for novel things in their environment,” remarked first author Joanna Spencer, a student in the Tri-Institutional M.D.-Ph.D. Program run by Rockefeller, Weill Cornell and Memorial Sloan-Kettering Cancer Center.

For the research, the scientists compared the performance of mice that had the regular BDNF gene and those with BDNF Met. They were pitted against each other on two main tasks mainly one that challenged them to memorize where an object was located in the cage and another that challenged them to identify the difference between similar objects which were placed in the cage in a gap of five minutes and 30 minutes.

It was discovered that the BDNF Met mice were significantly worse at both tasks. Aptitude for the object-placement test was apparently based on the stage of each mouse’s estrous cycle. Furthermore the scientists examined the hippocampus in the mice for hints about the anatomy underlying these differences. They appeared to have found that the variant gene overall produced more BDNF in addition to the cell receptor for BDNF, called TrkB. Those in the high-estrogen period of their cycle were revealed to have produced still more BDNF.

“Besides the potential value for better understanding PMDD, these findings add the BDNF system to our understanding of basic cellular and molecular mechanisms that underlie the ability of sex hormones such as estradiol to affect behavioral functions outside of reproduction, such as anxiety and memory,” says Bruce S. McEwen, head of the Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology at Rockefeller and senior author on the analysis.

According to the researchers, this might reflect an effort in the hippocampus to make up for a decrease of BDNF secretion that was put forth by other research in the neurons with the BDNF Met gene.

These results appear in a paper published in the Proceedings of the National Academy of Sciences.