In healthy humans, seasonality has been documented in psychological variables, chronotype, sleep, feeding, metabolic and autonomic function, thermoregulation, neurotransmission, and hormonal response to stimulation, thus representing a relevant factor to account for, especially when considering the individual susceptibility to disease. Mood is largely recognized as one of the central aspects of human behavior influenced by seasonal variations. This historical notion, already mentioned in ancient medical reports, has been recently confirmed by fMRI findings, which showed that seasonality in human cognitive brain functions may influence affective control with annual variations. Thus, seasonality plays a major role in mood disorders, affecting psychopathology, and representing the behavioral correlate of a heightened sensitivity to factors influencing circannual rhythms in patients. Although the genetic basis of seasonality and seasonal affective disorder (SAD) has not been established so far, there is growing evidence that factors affecting the biological clock, such as gene polymorphisms of the core clock machinery and seasonal changes of the light-dark cycle, exert a marked influence on the behavior of patients affected by mood disorders. Here we review recent findings about the effects of individual gene variants on seasonality, mood, and psychopathological characteristics.
L-glutamate is the major excitatory amino acid in the mammalian central nervous system (CNS). This neurotransmitter is essential for higher brain functions such as learning, cognition and memory. A tight regulation of extra-synaptic glutamate levels is needed to prevent a neurotoxic insult. Glutamate removal from the synaptic cleft is carried out by a family of sodium-dependent high-affinity transporters, collectively known as excitatory amino acid transporters. Dysfunction of glutamate transporters is generally involved in acute neuronal injury and neurodegenerative diseases, so characterizing and understanding the mechanisms that lead to the development of these disorders is an important goal in the design of novel treatments for the neurodegenerative diseases. Increasing evidence indicates glutamate transporters are controlled by the circadian system in direct and indirect manners, so in this contribution we focus on the mechanisms of circadian regulation (transcriptional, translational, post-translational and post-transcriptional regulation) of glutamate transport in neuronal and glial cells, and their consequence in brain function.
Circadian clocks are fundamental, time-tracking systems that allow organisms to adapt to the appropriate time of day and drive many physiological and cellular processes. Altered circadian rhythms can result from night-shift work, chronic jet lag, exposure to bright lights at night, or other conditioning, and have been shown to lead to increased likelihood of cancer, metabolic and cardiovascular diseases, and immune dysregulation. In cases of cancer, worse patient prognoses and drug resistance during treatment have also been observed. Breast, colon, prostate, lung, and ovarian cancers and hepatocellular carcinoma have all been linked in one way or another with altered circadian rhythms. Critical elements at the molecular level of the circadian system have been associated with cancer, but there have been fairly few studies in this regard. In this mini-review, we specifically focus on the role of altered circadian rhythms in breast cancer, providing an overview of studies performed at the epidemiological level through assessments made in animal and cellular models of the disease. We also address the disparities present among studies that take into account the rhythmicity of core clock and other proteins, and those which do not, and offer insights to the use of small molecules for studying the connections between circadian rhythms and cancer. This article will provide the reader with a concise, but thorough account of the research landscape as it pertains to altered circadian rhythms and breast cancer.
Frontiers in Neurology
Recanalization and Reperfusion Therapies of Acute Ischemic Stroke: What Have We Learned, Where Are We With Still Unanswered Questions, and Where Are We Headed?