Moderate UV Exposure Enhances Learning and Memory by Promoting a Novel Glutamate Biosynthetic Pathway in the Brain

Publication

Cell

Author(s)

Hongying Zhu, Ning Wang, Lei Yao, Qi Chen, Ran Zhang, Junchao Qian, Yiwen Hou, Weiwei Guo, Sijia Fan, Siling Liu, Qiaoyun Zhao, Feng Du, Xin Zuo, Yujun Guo, Yan Xu, Jiali Li, Tian Xue, Kai Zhong, Xiaoyuan Song, Guangming Huang, and Wei Xiong

Abstract

Sunlight exposure is known to affect mood, learning, and cognition. However, the molecular and cellular mechanisms remain elusive. Here, we show that moderate UV exposure elevated blood urocanic acid (UCA), which then crossed the blood-brain barrier. Single-cell mass spectrometry and isotopic labeling revealed a novel intra-neuronal metabolic pathway converting UCA to glutamate (GLU) after UV exposure. This UV-triggered GLU synthesis pro- moted its packaging into synaptic vesicles and its release at glutamatergic terminals in the motor cor- tex and hippocampus. Related behaviors, like ro- tarod learning and object recognition memory, were enhanced after UV exposure. All UV-induced meta- bolic, electrophysiological, and behavioral effects could be reproduced by the intravenous injection of UCA and diminished by the application of inhibitor or short hairpin RNA (shRNA) against urocanase, an enzyme critical for the conversion of UCA to GLU. These findings reveal a new GLU biosynthetic pathway, which could contribute to some of the sunlight-induced neurobehavioral changes.

Date

June 14, 2018

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