Signaling Pathway Behind Lethargy Identified

Orexin signaling pathway known to regulate sleep is also found to be responsible for inducing lethargy during illness, finds research.

This research is particularly meaningful because it implies that a new class of drugs developed to treat sleep disorders can reverse the inactivity and exhaustion brought on by acute illness. Although the sleep drugs were initially designed to treat narcolepsy, they have the potential to restore energy and motivation in patients with acute and chronic disease, the researchers report. Their findings are published in the The Journal of Neuroscience.

Narcolepsy - Overview Incidence Causes Symptoms Diagnosis Treatment Prognosis Prevention FAQs
Sleep is the blissful state that rejuvenates our mind and body everyday and any deprivation often leads to a disorder that can affect our health

"We all know what it means to feel 'bad' when we're acutely ill. In particular, patients with chronic diseases experience a compromise in motivated behaviors. They don't feel like getting up and doing anything. Yet the brain mechanisms behind this common experience have remained obscure," said Daniel L. Marks, M.D., Ph.D., principal investigator and associate professor of pediatrics in the Papé Family Pediatric Research Institute at OHSU Doernbecher Children's Hospital.

"Our lab has found that the neurotransmitter system thought to be primarily involved in the induction of sleep is actually extremely important in maintaining motivation and movement during acute and chronic illness," Marks explained.

Research has shown that in response to illness, animals divert all their energy to fight infection. Lethargy, fever and loss of appetite are symptoms of the body's highly organized strategy to sacrifice biological and physiological priorities to provide the greatest chance of survival.

Intensity of Sickness is All In The Genes
Two regions of the genome that affect the severity of cystic fibrosis have been identified by Johns Hopkins Institute for Genetic Medicine researchers

Although previous studies have identified the neurotransmitter system in the brain responsible for inducing fever and loss of appetite in response to disease, the mechanism for suppressing physical activity and motivation, and the means to treat it, has been unclear — until now.

To determine the cause of illness-induced lethargy, Marks and colleagues studied the brains of rats, the neuroactivity of which closely mimics human brains. They determined that acute and chronic inflammation-induced lethargy is brought about by a specific population of inflammation-sensitive neurons located near the neurotransmitter system that controls physical activity and arousal, known as the orexin system. When the researchers injected the rats with orexin, they were able to restore orexin signaling and, thus, restore motivated behaviors and movement.

Sleep Disorder Drugs Could Mitigate Exhaustion From Acute Illness
Sleep disorder drugs could mitigate exhaustion from acute illness. For a signaling system in the brain that regulates sleep is also responsible for inducing lethargy during illness.

This research demonstrates that orexin replacement is a viable therapeutic avenue for sickness-induced lethargy, the researchers explain. Because chronic disruption of this crucial neurotransmitter system leads to profound sleep disturbance and loss of motivated behaviors, they propose that drugs that mimic orexin would be useful in chronically ill patients to improve quality of life and independent living.

"There is a very exciting opportunity to quickly translate these findings into clinical practice," Marks said. "Because the role of orexin in sleep disorders like narcolepsy has been known for several years, the drug development efforts aimed at restoring orexin signaling are at an advanced state and nearly ready for clinical application."

Child Abuse Victims More Likely to Suffer Chronic Illnesses in Later Life
A new study suggests that those children who develop mental problems due to abuse are more likely to suffer from chronic illnesses later on in their lives.

Source-Eurekalert