Effects Of Moderate UV Exposure On A Novel Glutamate Biosynthetic Pathway In The Brain

Although excessive ultraviolet exposure is associated with several skin diseases,moderate UV exposure is beneficial for human health.For example,UVB light,one form of radiant energy from sunlight,promotes vitamin D generation in the skin.UV radiation has been used to treat certain diseases,such as psoriasis,atopic dermatitis,eczema,cutaneous T cell lymphoma,vitiligo and uremic pruritus.Interestingly,UV light not only causes peripheral effects,but also is associated with various neurological behaviors linked to the central nervous system.Specifically,moderate UV exposure has been shown to affect mood,addiction,cognition and memory.Chronic UV exposure results in alterations in levels of proteins,peptides and small molecules in the skin or blood,such as melanin,?-endorphin,vitamin D and nitric oxide.Mounting evidence suggests that these peripheral changes in chemical substances in the blood induced by UV exposure may affect the brain.For example,UV exposure elevates skin ?-endorphin,which may cross the blood-brain barrier,thus resulting in opioid-related antinociception and inducing addiction to UV light in mice.However,relatively little is known about the molecular and cellular mechanisms that mediate UV-induced neurobehavioral changes.Here,we showed that moderate UV exposure elevated blood urocanic acid(UCA),which then crossed the blood-brain barrier.UCA has been reported to exist only in the peripheral system,such as skin,liver,blood,and urine.In mammal liver and other peripheral tissues,UCA is an intermediate in the conversion of histidine to glutamate.The single-cell MS technology is a valuable tool to study metabolic pathways in the brain at the single-cell level.Single-cell mass spectrometry and isotopic labeling revealed a novel intra-neuronal metabolic pathway converting UCA to glutamate after UV exposure.This UV-triggered glutamate synthesis promoted its packaging into synaptic vesicles and its release at glutamatergic terminals in the motor cortex and hippocampus.Related behaviors,like rotarod learning and object recognition memory,were enhanced after UV exposure.All UV-induced metabolic,electrophysiological and behavioral effects could be reproduced by the intravenous injection of UCA and diminished by the application of inhibitor or shRNA against urocanase,an enzyme critical for the conversion of UCA to glutamate.These findings reveal a new glutamate biosynthetic pathway,which could contribute to some of the sunlight-induced neurobehavioral changes.