Scientists find on-off switch for stress in the brain
By William Smith
New research has important implications surrounding the understanding and treatment of anxiety disorders. Mental Healthy does not usually report on research which is not carried out on human beings, but the findings of this study are of sufficient interest we believe it worth reporting on.
Although the findings are a little difficult to follow for those of us who are not scientists, the implications encompass anxiety and other disorders such as post-traumatic stress disorder, schizophrenia, depression, epilepsy, bipolar disorder and autism.
The research was conducted by a team of scientists led by Dr. Gil Levkowitz of the Molecular Cell Biology Department. The findings explain that when we feel threatened, the brain centre which is responsible for response to threat goes into action. This sets of a chain of biochemical reactions which lead to the secretion of cortisol from the adrenal glands.
The researchers suggest that they have found an ‘on-off’ switch in the brain which regulates the production of a main biochemical signal from the brain which stimulates the production of cortisol in the body. The findings suggest that this is relevant to several stress-related neurological disorders.
The ‘on-off’ switch or signal is corticotropin releasing hormone (CRH). The hypothalamus is the part of the brain which stores CRH. This brain area senses danger and processes the information so that we can go into stress-response mode. Once the CRH-containing neurons have run out of their supply of the hormone they receive an order to produce more.
It was found that at several stages of CRH production, a protein called Otp is involved. Otp not only directly activates the genes which encode CRH but it also regulates the production of two receptors on the neurons’ surface which is responsible for receiving and relaying CRH production signals. This is what the researchers call the On-Off switches.
The team carried out their research on zebrafish and found that these two receptors are encoded in one single gene. The researchers explain this process by stating that Otp regulates a gene-edition process known as alternative splicing. This is how certain elements in the sequence encoded in a gene can be ‘cut and pasted’ to make slight differences.
The researchers state ‘In this case it generates two variants of a receptor called PAC1: The short version produces the On receptor, the long version, containing an extra sequence, encodes the Off receptor.’
The study found that the supply of CRH is replenished as the threat passes and the ratio between the two kinds of PAC1 receptor gradually changes from more ON to mostly OFF.
This work was done in collaboration with researchers from the Institute of Neurobiology Alfred Fessard at the Centre National de la Recherche Scientifique in France and also The Neurobiology Department. Together they found that blocking the production of the long receptor variant causes an anxiety-like behaviour in zebrafish.
They also found that the same alternatively-spliced switch in mice. They further suggest that this implies that with the mechanism being found and treated in both fish and mice, the same can also be done in the human brain.
The findings are published in ‘Neuron’.
