Robert Dantzer (who is an expert on sickness response/behaviour, a biologically-driven process) talked about orexin and its potential role in fatigue at the 2014 CMRC conference. My write up of his talk appeared on
Health Rising (Cort decided to add a few bits of his own).
Orexin – The key to Inflammation-related Fatigue
Professor Dantzer finished his presentation by describing a recently-discovered system in the hypothalamus of the brain that plays a key role in regulating energy levels – and could be a target for drugs to treat fatigue. The orexin system senses metabolic status and the balance between feeding and energy expenditure. It responds to glucose as well as leptin, a key molecule signalling energy levels that has been implicated in CFS/ME).
Is orexin the link between the metabolic and immune (leptin) problems in ME/CFS?
[Younger’s research suggests leptin, a substance tied to both metabolism and
microglial activation, could be a key driver of the immune activation found in ME/CFS. Younger, who is now director of the Neuroinflammation, Pain and Fatigue Lab at the University of Alabama, recently scored a major NIH grant to extend his research into leptin and immune activation in ME/CFS
The orexin system also plays a role in sleep versus wakefulness. Unlike healthy rats, those given LPS fail to become more active at night. What’s really interesting is that the reduction in activity correlates with reduced levels of orexin. However, rats given orexin as well as LPS don’t show any reduction in activity, suggesting that orexin plays a key role in activity levels.
Orexin as a Treatment for Fatigue?
Researchers suspected that orexin may play a similar role in the cancer-related fatigue resulting from chemotherapy. They found that giving mice chemotherapy did indeed lead to lower levels of activity, indicating fatigue and a reduction in their orexin levels.
Crucially, giving mice orexin alongside the chemo restored their activity levels, again suggesting reduced orexin played a central role in fatigue. He said that there are now drugs for narcolepsy targeting the orexin system, and perhaps they could one day be used for fatigue too.
Professor Dantzer said his group are working on a test of orexin as a treatment for cancer-related fatigue.
