Brain Science Advances

Sleep constitutes a third of human life and it is increasingly recognized as important for health. Over the past several decades, numerous genes have been identified to be involved in sleep regulation in animal models, but most of these genes when disturbed impair not only sleep but also health and physiological functions. Human natural short sleepers are individuals with lifelong short sleep and no obvious adverse outcomes associated with the lack of sleep. These traits appear to be heritable, and thus characterization of the genetic basis of natural short sleep provides an opportunity to study not only the genetic mechanism of human sleep but also the relationship between sleep and physiological function. This review focuses on the current understanding of mutations associated with the natural short sleep trait and the mechanisms by which they contribute to this trait.

Genetics is one of the various approaches adopted to understand and control mammalian sleep. Reverse genetics, which is usually applied to analyze sleep in gene-deficient mice, has been the mainstream field of genetic studies on sleep for the past three decades and has revealed that various molecules, including orexin, are involved in sleep regulation. Recently, forward genetic studies in humans and mice have identified gene mutations responsible for heritable sleep abnormalities, such as SIK3, NALCN, DEC2, the neuropeptide S receptor, and β1 adrenergic receptor. Furthermore, the protein kinase A-SIK3 pathway was shown to represent the intracellular neural signaling for sleep need. Large-scale genome-wide analyses of human sleep have been conducted, and many gene loci associated with individual differences in sleep have been found. The development of genome-editing technology and gene transfer by an adeno-associated virus has updated and expanded the genetic studies on mammals. These efforts are expected to elucidate the mechanisms of sleep–wake regulation and develop new therapeutic interventions for sleep disorders.

Many organisms, including humans, have evolved dynamic social behaviors to promote survival. Public health studies show that isolation from social groups is a major risk factor for adverse health outcomes in humans, but these studies lack mechanistic understanding. Animal models can provide insight into the molecular and neural mechanisms underlying how social isolation impacts health through investigations using genetic, genomic, molecular, and neuroscience methods. In this review, we discuss Drosophila melanogaster as a robust genetic model for studying the effects of social isolation and for developing a mechanistic understanding of the perception of social isolation and how it impacts health.

The paraventricular nucleus of the hypothalamus (PVH) acts as a cohesive functional unit that regulates neuroendocrine and autonomic function, complex behavior, and negative emotions after stress. However, how the PVH integrates arousal with these biological functions has only recently been explored. Clinical reports, combined with neurotoxic lesioning, immunochemistry, neuronal activity recordings, and the polysomnographic analyses of genetically modified animals, have revealed that the PVH is important for the control of wakefulness. Here, we review emerging anatomical and neural mechanisms for sleep–wake regulation in the PVH to support its essential role in the promotion and maintenance of wakefulness.

Age is recognized as the major factors of dementia, especially in for Alzheimer’s disease (AD). Given to the aged population, the increased number of demented population has been receiving a great impact in our society. Unfortunately, so far, no cured medicines have been demonstrated to provide effective treatment in AD. The combination of pharmacological and non-pharmacological interventions has been proposed to manage dementia with potential benefits especially in decreasing caregiver’s burden and behavior, as well as psychological problems of demented patients. Recently, giving to the glorious development in digital technologies, the virtual reality, one of the non-pharmacological interventions has been used extensively in dementia managements for its strengths which can be adapted in accordance with the heterogeneous needs from demented patients and their caregivers. However, various study designs and other reasons made these results difficult to be interpreted. In this review our goal is to provide a better understanding for these points.