With the advent of science and technology, India is achieving vast progress in the medical field. Due to this, it became possible to overcome many harmful diseases in the World. Now science has achieved one more achievement in the medical field that the researchers at the Tata Institute of Fundamental Research (TIFR) Mumbai have found a novel function for serotonin (a chemical that signals between neurons).
In the recent discovery, scientists have found that this serotonin helps in the production of new mitochondria (the powerhouse of the cell) in neurons, which increased the cellular respiration and fuel (ATP) in the cell. The scientists experimented this serotonin on mice and rats. If it finds success in humans, it will become an important medical implication.
The results of the study were published in the journal Proceedings of the National Academy of Sciences (PNAS). Prof. Vaidya recalls, “We cultured neurons and looked at the effects after adding serotonin, and found really unexpected results. We knew we had stumbled on something very interesting. These finds were confirmed and validated through extensive experiments.”
Serotonin’s chemical name is 5-hydroxytryptamine (5-HT). It is a monoamine neurotransmitter which means, it is a chemical in the brain that signals between neurons. It makes us calm, therefore, an increase in 5-HT may enhance individuals capacity to respond to stress. At the level of an organism, serotonin is known to be helpful in coping with stress. But, the underlying mechanism of its neuroprotective role was unknown.
The team of the scientists, jointly led by Vidita A. Vaidya and Ullas Kolthur-Seetharam from TIFR, with the support of Ashok Vaidya from KHS, provides insights into how serotonin generates more mitochondria thereby giving neurons the capacity to produce more energy and the ability to cope with stress better.
Prof. Vaidya said, “We found that serotonin reduces reactive oxygen species, thus providing neuroprotection against cellular stress. Serotonin can impact the manner in which neurons grapple with stress and affect the trajectory of aging.”
The major cause of neurodegenerative diseases is neuronal loss such as in Alzheimer’s and Parkinson’s. Abnormal mitochondrial functions result in neuronal death. The new findings from TIFR raise the possibility that mitochondrial abnormalities and neuronal loss could be prevented by serotonin signaling.
Neurons are not generated continuously unlike other cells and so identifying factors that increase mitochondrial health is key to prevent aging-associated neurological diseases.
Prof. Kolthur-Seetharam, a joint senior author of the paper, said, “Neurons exposed to serotonin not only produced more fuel (ATP), even the efficiency of mitochondrial output in these neurons was higher,”. This was seen in experiments done both in tissue culture and rats/mice.
Neurons have 14 receptors for serotonin, but only when serotonin binds to a specific receptor (5-HT2A) does it activate SIRT1 (a very important particular longevity factor/gene) that produce new mitochondria and more ATP in neurons.
Dr. Sashaina Fanibunda said, “Under in vitro conditions, neurons treated with a drug to block the 5-HT2A receptor as well as neurons that lacked the receptor abolished all the beneficial effects of serotonin on mitochondria. Further, in rats, activating the receptor using a drug enhanced the mitochondrial function.”
Beneficial effects of serotonin were seen by genetically increasing it in the brain of 13-to 15-month-old mice. Injecting serotonin directly into the brain of rats led to a direct increase in mitochondria number and ATP level.
Prof. Kolthur-Seetharam said, “With age, levels of serotonin, SIRT1, and mitochondria go down; the function of mitochondria also goes down. Thus supplying more serotonin could restore mitochondrial functions even in old mice.” Prof. Kolthur- Seetharam also said, “This study paves way for further research into designing therapeutic interventions by combined activation of serotonin and SIRT1 either through pharmacological approaches or coupling approved drugs that activate serotonin signaling with dietary interventions like calorie restriction. This may help tackle mood disorders and age-associated neurological decline.”