Researchers at Kolkata’s CSIR-Indian Institute of Chemical Biology (CSIR-IICB) have for the first time identified the molecular mechanism by which acute mental stress affects the stomach causing gastric ulcer or stress-related mucosal disease. Using a rat model subjected to cold-restrained stress, the research team led by Uday Bandyopadhyay from the Division of Infectious Diseases and Immunology at IICB has used drugs that can act specifically on mitochondria present in the stomach to prevent gastric ulcer caused by stress.
When subjected to stress, the mitochondrial respiratory capacity was disrupted, ATP production was reduced and oxidative stress increased. Stress also causes morphological changes to the mitochondria such as increased fragmentation. The results of the study were published in the journal Free Radical Biology and Medicine.
“Due to oxidative stress and fragmentation, the mitochondria in the gastric mucosal lining cannot behave in a normal fashion and ATP production gets further compromised. In the absence of ATP production, cells cannot proliferate and the gastric lining gets thinner due to mucosal cell death. All these cause stress-induced gastric ulcer,” explains Dr. Bandyopadhyay. “This is the first time we could find a link between the mind and mitochondria in the stomach. It is very exciting and fascinating.”
Second brain
The stomach is one of the organs most severely affected by stress and this is due to the link between the stomach and the brain. Moreover, the stomach is also known as the body’s second brain with a specialised neural network, repository of neurotransmitters and different kinds of nerve cells innervating the organ, though fewer in number.
Plenty of corticosterone was released into the blood when the animals were subjected to stress. Once corticosterone gets inside mitochondria it reduces ATP production and respiration capacity. By using a drug that prevents corticosterone from binding to the receptor found inside the cell, the researchers were able to significantly prevent stomach injury in the animals.
Interestingly, some common psychoactive drugs used in the study helped in preventing the pathological manifestations — gastric ulcer. “So we can say that it is indeed the acute mental stress which is causing gastric complications,” says Rudranil De from IICB and first author of the paper.
Role of mitochondria
“We delved deeper to find out the involvement of mitochondria in stress-induced gastric damage,” says De. A compound that scavenges harmful free radicals released from the malfunctioning mitochondria and another compound that inhibits mitochondrial fragmentation significantly prevented the injury and intra-gastric bleeding; although the drugs don’t reportedly act on the brain.
“Although stress is present, we could still prevent the damage caused to the stomach by targeting the mitochondria,” says De. “The use of these two compounds acting directly on the mitochondria confirmed that acute mental stress damages the mitochondria of the stomach ultimately leading to tissue injury and haemorrhage.”
The use of tranquilisers and barbiturates, often prescribed to patients suffering from mental stress and disorders, are associated with inherent problems including withdrawal effects and long-term side effects. “Our study proposes an alternative line of therapeutic strategy which relies on salvaging mitochondrial damage, thereby providing significant protection from stress. This will help avoid the use of existing psychoactive drugs while keeping the subjects alert,” says Somnath Mazumder from IICB, one of the authors.
If further research and human trials confirm the results seen in animal studies, it would lead to a new generation of anti-stress medications with minimal side effects which would aim at targeting the mitochondrial pathology to take care of a bigger psychosomatic health complication.
