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Estrogen binds to a specific protein - estrogen receptors, which are then attached to the ERE and thereby regulate gene activity. It has already been shown that estrogen influences the activity of the gene encoding the receptor PAC1.

Thus, there is quite a logical picture. Apparently, this site is really PAC1 gene estrogen-effector element. From what it is worth nucleotide - C or T, - dependent on the extent to which estrogen may influence the expression of this gene. From its expression, in turn, depends on the sensitivity of the cells to the hormone PACAP. Finally, the strength of the cell response to PACAP (and the concentration of PACAP) depends on the likelihood of developing PTSD.

The authors have tried to find a connection between this SNP and other mental disorders (depression, Alzheimer's disease, schizophrenia, bipolar disorder, drug addiction) - and found nothing. Apparently, this polymorphism has rather specific effects on the probability of affecting only women of PTSD.

Of all the symptoms of PTSD in women with CC genotype is most strongly expressed increased fearfulness (which is determined, in particular, on the physiological response to an unexpected sound, see: Political beliefs depend on fearfulness, "Elements", 26.09.2008).

In numerous other experiments the authors were able to establish the following facts:

1) The degree of methylation PAC1 receptor gene is positively correlated with the severity of PTSD symptoms, and this dependence - in contrast to all other - can be traced not only women but also men.

2) Levels of activity of the hormone gene PACAP and its receptor in the brain PAC1 inversely related: the higher the hormone, the receptor molecules made smaller, and vice versa. Such negative feedbacks are characteristic of many hormonal systems.

3) Development of mice fear conditioning (see: Neuroscientists figured out how to get rid of the terrible memories, "Elements", 25.11.2010) is accompanied by increased activity of PAC1 receptor gene in the amygdala (part of the brain plays a key role in shaping sustainable fear those or other conditional stimuli).

4) In experiments on rats have shown that increased levels of estrogen leads to an increase in the activity of genes hormone PACAP and its receptor PAC1 in the amygdala and other brain regions associated with fear.

Of course, to fully clarify the picture will need to make a lot more effort. However, the authors seem to have managed to find the first approach to deciphering the physiological bases of the increased tendency of women to the development of PTSD (as well as to the explanation of intersexual differences in the general level of fearfulness). The study may also have practical value: it showed that physicians and pharmacologists interested in developing drugs against PTSD, should pay attention to drugs that affect the system PACAP-PAC1.

Source: Kerry J. Ressler, Kristina B. Mercer, Bekh Bradley et al. Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor / /Nature. 2011. V. 470. P. 492-497.


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