Finnish researchers discover genetic mutation that reduces fear, anxiety and increases social interactions

Finnish researchers from the University of Eastern Finland and the University of Oulu have discovered a new type of gene mutation that reduces fear and anxiety and increases social interactions. The researchers used gene manipulation technology to remove the P4h-tm gene from the mouse genome and found an unexpected change in mouse behavior. P4h-tm knockout mice exhibited remarkable courage and a lack of acquired impotence compared to wild-type congenic mice possessing a functional P4h-tm gene. The results were published in neuropharmacology.

The researchers evaluated the mice with a large battery of behavioral tests including a new type of test for the panic reaction. The mice were placed in a sealed box filled with ordinary air and then 10% carbon dioxide. A high concentration of carbon dioxide induces an innate freezing reaction which, it seems, resembles the sensation of suffocation in patients suffering from panic attacks. P4h-tm knockout mice exhibited significantly less freezing than control mice in response to carbon dioxide exposure. In social interaction tests, the P4h-tm knockout mice established significantly more contact with another mouse than the controls. In addition, behavioral tests commonly used for screening anxiolytic and antidepressant drugs revealed a decrease in fear, anxiety, and acquired impotence in P4h-tm knockout mice. In addition, the study showed a link between brain anatomy and behavioral phenotype: the expression of the P4h-tm gene was particularly high in the amygdala, which plays a key role in the control of emotional reactions, including fear and anxiety.

The P4h-tm gene explains the transcription of the P4H-TM protein. This protein belongs to the family of prolyl-4-hydroxylases that play a central role in cellular adaptation to a sudden lack of oxygen. However, the P4H-TM protein differs from other prolyl-4-hydroxylases in its structure and unusual location (endoplasmic reticulum). The physiological role of the P4H-TM protein remains elusive despite years of intensive research, but is thought to have other effects on cell biology in addition to its adaptation to varying levels of oxygen. The research also tested the inactivation of three other known prolyl-4-hydroxylases in distinct mouse lineages. These mice did not show abnormal behavior in the tests mentioned above.

"Our results are really interesting, but according to a recent international study conducted by the University of the University, we know that the deficiency of the P4H-TM gene causes severe developmental defects in the body." Man, "said Professor Heikki Tanila of the University of Eastern Finland. note and continues: "However, in the light of current knowledge, we can not say whether these adverse effects result from embryonic development or whether they would also manifest themselves if the function of the P4H-TM protein was inhibited at the same time. 39, adulthood. "

"We could better find an answer to this question by using a conditional gene inactivation in which the gene could be disabled at any age," concludes Dr. Henri Leinonen, the first author of the article.

"In an ideal experiment, P4h-tm would only be deactivated in the amygdala of an adult mouse," adds Dr. Leinonen.

Although the striking effect of the inactivation of the P4h-tm gene on the emotional reactions of mice is still far from therapeutic application, it can quickly lead to the discovery of neurochemical mechanisms regulating emotions and the development of new anti-anxiety drugs and antidepressants. Anxiety disorders and depression are a huge global problem. According to the World Health Organization (WHO), nearly 300 million people worldwide suffer from anxiety disorders and more than 300 million people suffer from depression.