Reduced melatonin levels may facilitate glioblastoma initiation in the subventricular zone

Abstract There is increasing evidence that glioblastoma, a highly aggressive brain tumour, originates from a neural stem cell (NSC) located in the subventricular zone (SVZ) of the lateral cerebral ventricle. Using the most advanced in vivo imaging techniques, Gengatharan and colleagues recently identified a day/night difference in the adult SVZ-NSC division. They reported that the circadian melatonin rhythm and its receptor control the day/night difference in NSC division with high mitotic activity during the day and low activity at night. Expression of melatonin and its receptor diminishes during ageing, which eliminates the regulatory effect of melatonin on NSC mitosis. Moreover, the circadian melatonin rhythm is dampened by light-at-night with the potential of altering the circadian mitotic cycle of NSC in the SVZ. Also, men with a lower melatonin amplitude than women exhibit a 60% higher rate of glioblastoma incidence. Given that ageing contributes significantly to glioblastoma initiation and progression, we suggest that the decline in circadian melatonin synthesis and release as well as its receptors in the SVZ, which also diminish with an ageing act in concert with other factors to facilitate glioblastoma initiation and growth.