Research sheds light on treatment for sleep disorders
Researchers partially funded by the EU have made advances in understanding the cellular and molecular pathways affected by sleep deprivation. With millions of people regularly suffering from a lack of sleep, the findings could have significant social and clinical applications. EU support for the research came from the THERA-CAMP ('Identification of therapeutic molecules to target compartmentalised cAMP signalling networks in human disease') project, which was financed under the 'Life sciences, genomics and biotechnology for health' Thematic area of the Sixth Framework Programme (FP6). Publishing in the journal Nature, the scientists explain how they identified a molecular mechanism by which brief sleep deprivation alters hippocampal function. In the brains of humans and other mammals, the hippocampus has, among other roles, an important part to play in such cognitive functions as long-term memory and spatial navigation. Drugs which enhance the molecular mechanism investigated by the researchers could provide a new therapeutic approach to counteract the effects of sleep deprivation on these functions. The hippocampus has a form of neural plasticity, known as long-term potentiation (LTP), which enhances neural signal transmissions. Researchers looked at this plasticity in mice which were deprived of sleep for varying periods. Male mice were housed individually on a 12 hour cycle of lightness and darkness for 6 days. They were then divided into two groups. Mice from the sleep-deprived group were gently handled for five hours, while the second group was left undisturbed. Researchers found that sleep deprivation lead to higher levels phosphodiesterase 4 (PDE4). PDE4 breaks down another molecule called cAMP (cyclic adenosine monophosphate) which plays an important role in maintaining the plasticity of the mouse hippocampus. For contextual fear conditioning experiments, the mice were placed in a new chamber for three minutes, and received a light shock after two and a half minutes. Half of the mice were then deprived of sleep for five hours. Mice received one of two drugs immediately and two and a half hours after the shock. Researchers then tested the mice for contextual memory for two periods after the shock and drug treatments. Of the mice who were given drugs, those who received phosphodiesterase inhibitors showed recovery from the sleep-deprivation-induced deficits in hippocampal plasticity and hippocampus-dependent memory. This finding shows that brief sleep deprivation disrupts hippocampal function by interfering with cAMP signalling through increased PDE4 activity. Drugs that enhance cAMP signalling may provide a new therapeutic approach to counteract sleep deprivation's effects on specific cognitive mental processes such as comprehension, inference, decision-making, planning and learning. The study states that the findings will 'lay the groundwork for future analysis of the functional biochemistry of sleep deprivation and the development of new therapeutics to ameliorate the effect of sleep deprivation.'
Countries
Netherlands, United Kingdom, United States