Transcranial light alters melanopsin and monoamine production in mouse (Mus musculus) brain

Abstract Background: The mammalian circadian system sets a rhythm for the appropriate occurrence of physiological and behavioral phenomena during a 24-h period. Since the duration of the circadian system is usually less or more than 24 h, it must be entrained regularly and light is the governing stimulus of the rhythm. The target for light stimulus is the master circadian clock, which is located in the suprachiasmatic nucleus in the hypothalamus. One of the key molecules transmitting light information and entraining the clock is melanopsin (OPN4), a G protein-coupled molecule that is found most abundantly in the retina and brain. Although light stimulus is usually mediated through the eyes, light has an ability to penetrate the skull. Here, we present the effect of transcranial light illumination on OPN4 and serotonin expression in the mouse brain. Methods: Male mice were randomly assigned to a control group, morning-light group and evening-light group, and animals were illuminated transcranially five times a week for 8 min for a total of 4 weeks. The concentrations of OPN4 and monoamines were analyzed with Western blot and high-performance liquid chromatography (HPLC) techniques, respectively. Results: Our results show that transcranial light illumination increases the amount of OPN4 in the hypothalamus and cerebellum. Additionally, the production of serotonin in the cortex was shown to decrease in the morning-light group. Conclusions: With this study, we provide novel information on the effects of light administration through the skull on transmitters regulating circadian rhythmicity by showing that transcranial light affects molecules involved in circadian rhythmicity

Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families

Complex traits, including migraine, often aggregate in families, but the underlying genetic architecture behind this is not well understood. The aggregation could be explained by rare, penetrant variants that segregate according to Mendelian inheritance or by the sufficient polygenic accumulation of common variants, each with an individually small effect, or a combination of the two hypotheses. In 8,319 individuals across 1,589 migraine families, we calculated migraine polygenic risk scores (PRS) and found a significantly significantly higher common variant burden in familial cases (n = 5,317, OR = 1.76, 95% CI = 1.71-1.81, p = 1.7 x 10(-109)) compared to population cases from the FINRISK cohort (n = 1,101, OR = 1.32, 95% CI = 1.25-1.38, p = 7.2 x 10(-17)). The PRS explained 1.6% of the phenotypic variance in the population cases and 3.5% in the familial cases (including 2.9% for migraine without aura, 5.5% for migraine with typical aura, and 8.2% for hemiplegic migraine). The results demonstrate a significant contribution of common polygenic variation to the familial aggregation of migraine