TRPC5 belongs to a group of genes involved in detecting sensory signals from heat, taste, and touch. In particular, TRPC5 acts on a pathway in the hypothalamus, where it is thought to control appetite.
The impetus for the current study came after finding two boys from different families with severe obesity, anxiety, autism, and behavioral problems triggered by sounds or smells who were missing the TRPC5 gene. Further study revealed that the boys inherited the gene deletion from their mothers, who also had obesity and had experienced postnatal depression.
To understand more about whether TRPC5 was linked to the observed health issues, the researchers studied mouse models that were genetically engineered to have a defective version of the gene. Ultimately, they found that male mice with the defective gene had similar problems as the boys including weight gain, anxiety, a dislike of social interaction and aggressive behavior.
Female mice displayed the same behavior however, when they became mothers, also developed depressive behavior and impaired maternal care. Depressive behavior was neither observed in male or female mice who were not mothers.
“What we saw in those mice was quite remarkable. They displayed very similar behaviours to those seen in people missing the TRPC5 gene, which in mothers included signs of depression and a difficulty caring for their babies. This shows us that this gene is causing these behaviours,” said study author, Dr. Yong Xu, Associate Director for Basic Sciences at the USDA/ARS Children’s Nutrition Research Center at Baylor College of Medicine, in a press release.
From closer study of the hypothalamus, the researchers found that TRPC5 acts on oxytocin neurons. Oxytocin is commonly known as the 'love hormone’ as it is released in response to displays of affection, emotion, and bonding. Deleting the gene from oxytocin neurons led to otherwise healthy mice displaying similar signs of anxiety, overeating, and impaired sociability, and for mothers: postnatal depression. Restoring the gene reduced body weight and symptoms of anxiety and postnatal depression.
“There’s a reason why people lacking TRPC5 develop all of these conditions. We’ve known for a long time that the hypothalamus plays a key role in regulating ‘instinctive behaviours’ – which enable humans and animals to survive – such as looking for food, social interaction, the flight or fight response, and caring for their infants,” said study author Professor Sadaf Farooqi from the Institute of Metabolic Science at the University of Cambridge in a press release.
“Our work shows that TRPC5 acts on oxytocin neurons in the hypothalamus to play a critical role in regulating our instincts,” added Farooqi.
TRPC5 deletions are rare; a DNA analysis found that just 369 out of 500,000 individuals carried variants of the gene and had a higher-than-average body mass index. The findings nevertheless suggest that restoring oxytocin could help treat people with missing or defective TRCP5 genes.
Sources: Neuroscience News, Cell