Yu Xiang's team reveals the mechanisms that DHA promotes neurodevelopment in the brain.

The formation of functional synapses is highly dependent on the formation of functional synapses, and this process is regulated by intracellular and extracellular signals.docosahexaenoic acid (DHA) is an important component of the plasma membrane of neurons: in the gray matter area of the cerebral cortex, 30% - 40% of the fatty acids in the plasma membrane phospholipids are DHA.DHA mainly exists in plasma membrane phospholipids in the form of esterification. At the same time, DHA can also be released from the membrane under the action of phospholipase. DHA participates in a variety of signal transduction in a free way or through its derivatives.studies have shown that free DHA may be an in vivo receptor for RXR, but there has been a lack of functional association.a large number of studies have shown that DHA deficiency is associated with a variety of neurodevelopmental disorders and neuropsychiatric diseases, and DHA supplementation is believed to alleviate or treat developmental retardation and neuropsychiatric diseases, and even improve the cognition of normal people.however, it usually takes a long time for dietary DHA to promote synaptic function and cognitive behavior, which takes weeks in mice and months or lacks visible effects in humans. This is far from the effect of adding non esterified DHA (free DHA) to cultured neurons in vitro, which can promote the development and function of synapses within hours to days [1-3] 。therefore, it is very important to further explore the mechanism of DHA promoting brain development and function.on May 19, 2020, the research team of Yu Xiang, Center for excellence in brain science and intelligent technology / Institute of neuroscience, Chinese Academy of Sciences (currently working in school of life sciences, Peking University), published a research paper entitled retinoid X receptor α regulates DHA dependent spinogenesis and functional synapse formation in vivo on cell reports online.it was found that the development of dendritic spines and functional synapses could be regulated by non esterified DHA (free DHA) in vivo through rxra dependent signal pathway. The new mechanism of DHA promoting brain development and function was analyzed, and a new idea for the treatment of related diseases was provided.in this work, the researchers found that the loss of rxra and the inhibition of DHA release could lead to the decrease of dendritic spine density and excitatory synaptic transmission, and the overexpression of rxra and the supplement of unesterified DHA could increase the density of dendritic spines and excitatory synaptic transmission.in addition, the promotion effect of non esterified DHA depends on the expression of rxra.the researchers further found that rxra knockout and non esterified DHA supplementation could inhibit and promote the expression of immediate early genes respectively, suggesting that rxra and DHA may affect synaptic development through positive feedback regulation of immediate early genes.this study provides in vivo evidence that DHA and rxra act as ligand receptor combinations to regulate the development of dendritic spines and the formation of functional synapses, and analyzes the new mechanism of DHA promoting brain development and function.the results of this study highlight the important role of free DHA.interestingly, studies have shown that exercise and DHA supplement complement each other in promoting synaptic function, suggesting that exercise may increase the production of free DHA [4,5].Dr. Cao Huateng and Dr. Li minyin of Yuxiang research team are the first authors of the paper. Dr. Li Guangying, Dr. Li Shujing, Lu Yuan and Wen Bincheng have also made important contributions.note: the mechanism of DHA and rxra in regulating synaptic development. Under the action of specific phospholipase ipla2, DHA is released from the plasma membrane to form free DHA; it binds its receptor rxra in the nucleus to promote the expression of immediate early genes; then promotes the development of dendritic spines and the formation of functional synapses, and finally promotes cognitive and behavioral performance. Bazinet, R.P. and S. lay, polyunsaturated fatty acids and their metals in brain function and disease. Nat Rev Neurosci, 2014.15 (12): P. 771-85.2. Lauritzen, L., et al., DHA effects in brain development and function. Nutrients, 2016.8 (1): P. 6.3. Tanaka, K., et al., effects of effects of brain development and function docosahexaenoic Acid on neurotransmission. Biomol Ther (Seoul), 2012. 20(2): p. 152-7.4. Chytrova, G., Z. Ying, and F. Gomez-Pinilla, Exercise contributes to the effects of DHA dietary supplementation by acting on membrane-related synaptic systems. Brain Res, 2010. 1341: p. 32-40.5. Wu, A., Z. Ying, and F. Gomez-Pinilla, Docosahexaenoic acid dietary supplementation enhances the effects of exercise on synaptic plasticity and cognition. Neuroscience, 2008. 155(3): p. 751-9.