Hefei National Laboratory for Physical Sciences at the Microscale, Neurodegenerative Disorder Research Center, School of Life Sciences, University of Science and Technology of China, 230026 Hefei, China; Hefei National Laboratory for Physical Sciences at the Microscale, School of Chemistry and Materials Science, University of Science and Technology of China, 230026 Hefei, China.
Hefei National Laboratory for Physical Sciences at the Microscale, Neurodegenerative Disorder Research Center, School of Life Sciences, University of Science and Technology of China, 230026 Hefei, China.
Cell. 2018 Jun 14;173(7):1716-1727.e17. doi: 10.1016/j.cell.2018.04.014. Epub 2018 May 17.
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 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 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.
阳光照射已知会影响情绪、学习和认知。然而，其分子和细胞机制仍难以捉摸。在这里，我们表明适度的 UV 照射会提高血液中的尿刊酸（UCA）水平，然后 UCA 穿过血脑屏障。单细胞质谱和同位素标记显示，在 UV 照射后，UCA 会转化为谷氨酸（GLU），这是一种新的神经元内代谢途径。这种由 UV 触发的 GLU 合成促进了其包装到突触小泡中，并在运动皮层和海马体的谷氨酸能末梢中释放。UV 照射后，相关行为，如旋转棒学习和物体识别记忆，得到增强。静脉注射 UCA 可以重现所有由 UV 引起的代谢、电生理和行为效应，而应用尿刊酸酶抑制剂或短发夹 RNA（shRNA）则会减弱这种效应，尿刊酸酶是将 UCA 转化为 GLU 的关键酶。这些发现揭示了一种新的 GLU 生物合成途径，它可能有助于解释一些阳光引起的神经行为变化。
