The gene neuromedin U (Nmu) regulates sleep, according to a study published in the journal Neuron on Feb. 17. Caltech biologists claim that their study can lay the foundation to new sleep disorder treatments.
David Prober, assistant professor of biology at Caltech, says that the zebrafish that have overactivated Nmu, expressed in the hypothalamus, are more active during the day and night and did not sleep at all. Moreover, the gene is also called nature’s stimulant because the fish that lacked it took longer to wake up in the morning and were less active during the day.
The researchers chose the zebrafish because these start to wake up at the end of the night and then become much more active when the lights turn on. The biologists then injected their embryos with a plasmid, a DNA molecule, that carried the genes the team wanted to find out that regulates sleep. They were able to control the gene’s expression through a genetic switch called heat-shock promoter, which turned on when the fish were heated to about 37 degrees Celsius.
After discovering the gene’s effects, the team wanted to find out what would happen if the fish did not have it so they mutilated the zebrafish and noticed that the larvae without Nmu were less active during the day and the adult fish became sluggish especially in the morning.
Researchers previously thought that Nmu acts through the hypothalamic-pituitary-adrenal (HPA) axis, the stress response pathway. However, the zebrafish did not have the glucocorticoid receptor, a protein necessary for HPA axis signalling, which suggested that the gene does not act through the axis.
Instead, they realised that the corticotrophin-releasing hormone (CRH) signalling in the brainstem is needed to enable the Nmu affect in its behaviour. When the CRH is blocked, the wake-promoting effects of Nmu were also blocked. Prober also notes that CRH is important for normal activity levels.
“That was surprising because CRH is the gene that initiates the HPA axis response, but the cells that do that are in the hypothalamus, a different part of the brain, aren’t activated when we overexpress Nmu,” adds Prober. “It’s another population of CRH cells in the brainstem that are activated by Nmu overexpression.”