New research from Italy that is based on studies in mice found that Sudden Infant Death Syndrome (SIDS) may be linked to an imbalance in the brain signalling chemical serontonin that regulates heartbeat and breathing, and if shown to be true of humans could point to a way to identify babies at risk of SIDS.
The study was the work of corresponding author Dr Cornelius Gross, a researcher at the European Molecular Biology Laboratory (EMBL) based in Monterotondo, Italy, and colleagues, and is published in the 4th July issue of Science.
SIDS, also known as cot death, is the leading cause of death of babies in the developed world; killing over 2000 infants in the US alone in 2005. It strikes seemingly healthy babies between one and 12 months old. Postmortem studies have revealed alterations in serotonin-signalling neurons in the brainstem of such infants, but the underlying mechanisms by which imbalance in serotonin might lead to sudden death is still a mystery.
Gross and colleagues were studying genetically altered mice that had an overexpressed receptor that regulates serotonin signalling, the serotonin 1A autoreceptor.
Gross said in a statement from EMBL that at first the mice appeared normal, but after a while they started to show “sporadic and unpredictable drops in heart rate and body temperature”, and more than half of the mice died from these crises during a particular time window in early life. It was when they saw these symptoms that the possibility of SIDS first came to them, said Gross.
Perhaps a genetic predisposition to serotonin imbalance could be an underlying factor in causing SIDS, suggested the researchers.
Neurons that communicate using serotonin send signals to spinal cord nerve cells that regulate the heart and other organs that play an important role in maintaining body temperature. This signalling mechanism was disrupted in the genetically altered mice and could be observed by various tests, such as when placed in a cold environment they could not activate the brown fat tissue that produces heat.
Interestingly, death does not result when serotonin is blocked completely, only when its delicate balance is upset, as it is when the serotonin 1A autoreceptor is overexpressed. It would seem that a negative feedback cycle develops that reduces serotonin levels and gradually dampens down the signals that regulate vital body functions.
The authors were cautious about drawing parallels with SIDS in humans, where serotonin imbalance may not have exactly the same effect; but the mouse model discovery does add another piece to the jigsaw in that it suggests disruption of this life-essential signalling pathway could be an underlying contributor.
Co-author Enrica Audero, who did the research in the lab run by Gross, said:
“We hope the mouse model will help identify risk factors for SIDS.”
“One open question is whether like in SIDS, the animals die during sleep and whether we can identify which mice will die by looking at their heart rate or body temperature before the crisis,” added Audero.
Professor of psychiatry and pediatrics at Columbia, Dr William Fifer, who advised the authors, said research on SIDS has been “painstakingly slow”.
“This is one more significant source of information that shows that serotonin deficiency may be the key in SIDS,” said Fifer.
“Sporadic Autonomic Dysregulation and Death Associated with Excessive Serotonin Autoinhibition.”
Enrica Audero, Elisabetta Coppi, Boris Mlinar, Tiziana Rossetti, Antonio Caprioli, Mumna Al Banchaabouchi, Renato Corradetti, and Cornelius Gross
Science 4 July 2008, Vol. 321, No 5885, pages 130 – 133.
DOI: 10.1126/science.1157871
Source: Journal abstract, EMBL.
Written by: Catharine Paddock, PhD