The Center for Brain Intelligence Excellence reveals DHA's mechanisms that promote neurodevelopment almost in the brain.

On May 19, cell reports online published a research paper entitled "in vivo mechanism of retinol like X receptor α regulating DHA dependent dendritic spine development and functional synaptic formation", which was completed by the research group of Yu Xiang, Center for excellence and innovation of brain science and intelligent technology, Chinese Academy of Sciences (Institute of Neuroscience) and State Key Laboratory of neuroscience.in combination with in vivo gene manipulation (transgenic mice, virus injection and embryo electroporation), pharmacology, fluorescent dye microinjection, RNA sequencing, brain electrophysiology and behavior experiments, it was found that free DHA in the brain regulates the development of dendritic spines and functional synapses through rxra dependent signal pathway, and analyzed the new mechanism of DHA promoting brain development and function The treatment of diseases provides new ideas.the formation of neural circuits 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 the plasma membrane phospholipids in the form of esterification, but it can also be released from the membrane under the action of phospholipase, and participate in a variety of signal transduction in a free way or through its derivatives.studies have shown that free DHA is an in vivo receptor of retinol like X receptor (RXR), but there has been a lack of functional correlation.nuclear receptor rxra has been reported to be associated with cognitive ability and the occurrence and development of some neurological diseases.a large number of studies have shown that DHA deficiency is associated with a variety of neurodevelopmental disorders and neuropsychiatric disorders, and DHA supplementation is considered to be able to alleviate or treat developmental delay or neuropsychiatric disorders, and even enhance the cognition of normal people.however, the effects of dietary DHA supplementation on synaptic function and behavioral performance require a long period of time, which takes weeks for mice and months for humans; this is far from the effect of adding non esterified DHA (free DHA) to cultured neurons in vitro to promote synaptic development and synaptic transmission within hours to days.therefore, it is very important to further explore the mechanism of DHA in promoting brain development and function in vivo.according to the known phenomenon, Yu Xiang's research group proposed the hypothesis that the development of synapses may be regulated by the receptor rxra of non esterified DHA in vivo.the density of dendritic spines in vertebral neurons was significantly reduced in rxra CKO mice, which specifically knockout rxra in the cerebral cortex and hippocampal excitatory neurons.they also found that rxra regulates the development of dendritic spines and functional synapses in a bidirectional, postsynaptic and cellular manner, and its function depends on its DNA binding domain.consistent with the bidirectional regulation of rxra, intraventricular injection of non esterified DHA can significantly increase the density of dendritic spines, and specific inhibition of DHA release can significantly reduce the density of dendritic spines; importantly, DHA injection into the brain of rxra CKO mice can not promote the development of dendritic spines.in addition, the expression of immediate early genes (IEGs), an important regulator of synaptic development, was decreased in rxra Kko mice, while the expression of immediate early genes was increased by intracerebral injection of DHA.finally, they tested the basic behavior of rxra CKO mice and found that most of the behaviors were normal, but the behaviors related to social memory were significantly abnormal.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. It also analyzes the new mechanism of DHA promoting brain development and function, and provides new ideas for the treatment of related brain diseases.under the guidance of researcher Yu Xiang, this work is mainly completed by doctoral students Cao Huateng and Li minyin. Postdoctoral students li Guangying, Li Shujing, Lu Yuan and Wen Bincheng also have important contributions.the project is supported by the Ministry of science and technology, NSFC, Chinese Academy of Sciences and Shanghai municipal government.note: the mechanism of DHA and rxra in regulating synaptic development.Under the action of specific phospholipase iPLA2,DHA releases free plasma from the plasma membrane, promotes the expression of early genes in the nucleus and combines its receptor RXRA, thereby promoting the development of dendritic spines and functional synapses, and finally promotes cognitive and behavioral performance. 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