Mechanisms underlying eustress under cyclic environment
Adaptive stress response to environmental changes is important to maintain homeostasis. The response can cause both negative (distress) or positive (eustress) effects on the body. The eustress leads to resilience to diseases and promotes health, but neurobiological mechanisms remain unclear.
Out lab has been identified an animal model of eustress by using cyclic environmental changes. We are trying to clarify the molecular and physiological mechanisms underlying eustress.
Mechanisms underlying internal desynchrony of the circadian clock under social jetlag
The circadian clock is the endogenous clock that drives approximately 24 h rhythms in the body. The master clock resides in the suprachiasmatic nucleus in the hypothalamus, which orchestrates peripheral clocks in other brain regions and peripheral organs. In the modern society, the circadian clock can be often disrupted by shiftwork, irregular lifestyles, and frequent shift of light-dark cycles. The circadian disruption is deeply related to increased risks of many diseases, such as cancer, obesity, diabetes, hypertension, and psychiatric diseases.
A popular type of the circadian disruption is “social jetlag”, which is the discrepancy of sleep patterns betweenweekdays and weekends. It causes misalignment of internal clock phase and social time, leading jet lagged conditions such as fatigue and tiredness. Recent studies have clarified the close association between social jetlag and obesity, depression, and cognitive ability.
Our lab addresses mechanisms underlying circadian disruption (internal desynchrony) in social jetlagged mouse model. We are also trying to find functional nutrients or food factors to improve or prevent social jetlag.
Chrononutrition, amino acids, and brain functions
Chrononutrition is the study of the interaction between biological clocks and diet/nutrition. Our lab focuses on the effect of diet timing on brain functions and the effect of amino acids on the circadian clocks, using animal models and immortalized cells.
1. Diet timing and brain functions
Inappropriate timing of food intake, including skipping breakfast, late dinner, or nightsnacks, is associated with disruption of the circadian clock, and increases risks of various diseases. Studies have shown that time-restricted feeding during appropriate time can prevent risks of metabolic diseases.
Our lab addresses the effect of time-restricted feeding on memory and leaning behaviors, signaling molecules in synaptic plasticity, and neuronal morphology in mice. In the modern society, a number of people have difficulties in keeping regular dietary rhythms due to various lifestyles, shiftwork, or nursing. We aim to find functional nutrients or food factors that prevent the deleterious effect of inappropriate dietary rhythms.
2. Amino acids and the circadian clock
Amino acids have various functions in the body, such as sleep promotion, stress regulation, and hormonal regulation. We have identified that L-serine can enhance the light-induced circadian clock phase resetting in mouse and humans (Yasuo et al., Journal of Nutrition, 2017) and that L-ornithine can modify secretion rhythms of growth hormone, melatonin, and corticosterone in mice (Matsuo et al., Chronobiology International, 2015）. We further elucidate bioregulatory mechanisms of several amino acids using animals and cells.
Effect of early-life photoperiod on growth, metabolism, and brain development
Seasonal changes in photoperiod influence animal behaviors, metabolism, immune functions, and reproduction. In humans, photoperiod is related to seasonal affective disorder (SAD, winter depression), which is a subtype of major depressive or bipolar disorder that follows a seasonal pattern of major depressive episodes that occur at a specific time of the year.Additionally, birth seasons affect life-time risks of psychiatric/neurological diseases.
Our lab has been addressed the mechanisms and nutritional treatment of winter depression by using a mouse model (Tahiguch et al., Behavioural Brain Research 2021; Otsuka et al., Psychoneuroendocrinology, 2014; British Journal of Nutrition, 2015). We also clarified that photoperiod in early life stages affect growth, metabolism, and neuronal proliferation and differentiation (Takai et al., Neuroscience, 2018; Uchiwa et al., Physiological Reports, 2016).
Currently we are elucidating epigenetic mechanisms underlying the programming effect of early-life photoperiod on brain and body. We are also expanding the study to domestic animals; we are studying the effect of photoperiod on Japanese Black beef cow in collaboration with farm researchers.