Editorial [Hot Topic:Neurobiology Wakes Up for Research on Sleep Disorders: An Integration of Basic and Clinical Research(Executive Editor: Luigi De Gennaro)]

On average we spend one third of our lives asleep, and we have little idea why. Similarly, despite the high prevalence of sleep disorders and their negative impact on waking functions and life quality, which significantly contribute to healthcare costs, most basic pathophysiological mechanisms are still unknown. Knowledge accumulated in recent years about the identification of susceptibility genetic determinants, about biochemical mechanisms of sleep regulatory substances, and about initiation of sleep at circumscribed local neural networks level, has led to a new integration between findings of basic and clinical research. Hopefully, these will also have an impact on a better understanding of pathogenesis of sleep disorders, on an assessment of the risk for diseases, and on new drug development to treat and to prevent the underlying conditions. In basic sleep research, the consolidated evidence of a robust and reliable marker of sleep need, the amount of electroencephalogram (EEG) slow wave activity (SWA) during non-rapid eye movement (NREM) sleep, provided the best working model of sleep regulation [1]. According to the 2-process model of sleep regulation, SWA depends on the duration of previous wakefulness, and represents a marker of NREM sleep intensity; manipulations of sleep pressure lead to clear homeostatic recovery processes [1, 2]. Recent research, however, has shown that these recovery processes are mainly local and do not involve the entire cerebral cortex [3, 4]. Furthermore, experience-dependent plasticity in specific neural circuits during wakefulness induces localized changes in SWA during subsequent sleep [5, 6], supporting the idea that sleep regulation is a locally regulated process. This emerging notion of sleep as a local process could help to shift the focus of clinical sleep research from structural to functional characteristics of sleep disorders. We strongly believe that the extension of the theoretical framework of “local sleep” to the study of sleep disorders has a great heuristic potential. Likewise, the growing body of evidence pointing to (a) genetic determinants of normal and pathological sleep, in humans and in animals [7], which may be also responsible for the large individual differences in normal sleep [8], are candidates for a similar heuristic potential. Thanks to Prof Banks invitation to edit a special issue of Current Pharmaceutical Design, I was able to assemble an outstanding panel of experts, each addressing a different segment of the wide spectrum of neurobiological mechanisms of sleep disorders. This issue consists of 9 carefully selected peer-reviewed articles prepared by some of the leading experts in the field of sleep and its disorders. I trust this issue will be of great interest to the readers of Current Pharmaceutical Design and will expose them to the exciting field of sleep and its disorders. Drs. Dauvilliers and Tafti [8] reviewed the role of genetic basis in the key sleep disorders. Recent linkage, genome-wide and candidate gene association studies resulted in the identification of gene mutations, gene localizations, or evidence for susceptibility genes and/or loci in several sleep disorders. These identified susceptibility genetic determinants will provide clues to a better understanding of the pathogenesis of sleep disorders, to assess not only the risk for diseases but also to develop therapeutic agents for treating and preventing the underlying conditions. With similar aims, Dr. Landolt's [9] review focused on the molecular mechanisms underlying the trait-like, inter-individual variation in sleep regulation, with a special attention to the role of adenosine in sleep homeostasis and its implications for the neurobiology of sleep-wake disorders and their pharmacological treatment. This is followed by Dr. Krueger's [10] that shows that sleep is a local use-dependent process influenced by cytokines and their effectors' molecules such as nitric oxide, prostaglandins and adenosine. The article opens a new avenue to explain physiological sleep, and sleep disturbances within the context of the brain cytokine network. Dr. Nofzinger [11] reviews the functional neuroimaging findings in patients with sleep disorders, and studies addressing the pharmacology of sleep disorders. These findings may be helpful in clarifying pathophysiology, aiding in differential diagnosis, in assessing treatment response, guiding new drug development, and monitoring treatment response.