Science: Sperm miRNA-mediated inheritance of depression

Science: Sperm miRNA-mediated inheritance of depression.   In view of the fact that the onset of depression is the result of the close interaction of genetic and environmental factors, it is very consistent with the characteristics of intergenerational inheritance, suggesting that the genetic law of depression may be explained from the perspective of intergenerational inheritance.

Depression is the most common mental disorder in the population. It is called the “cold in psychiatry”. There are 120 to 200 million patients worldwide. The biological etiology and pathogenesis of depression are still unclear, but it is generally believed that its onset is the result of the combined effect of genetic and environmental factors. Nowadays, classical genetics are used to explore the genetic rules and susceptibility genes of depression. Certain obstacles, no genes clearly related to the inheritance of depression have been found. Therefore, it is suggested that it is necessary to explore, discover and solve the genetic problems in depression from a new genetics direction and angle.

More and more evidence shows that our life experiences, external stimuli, and eating habits will be “imprinted” in our germ cells in an epigenetic manner, and then affect offspring through intergenerational inheritance. Epigenetic factors including DNA methylation, histone modification, and non-coding small RNAs have been found to mediate the occurrence of intergenerational inheritance.

In view of the fact that the onset of depression is the result of the close interaction of genetic and environmental factors, it is very consistent with the characteristics of intergenerational inheritance, suggesting that the genetic law of depression may be explained from the perspective of intergenerational inheritance.

On February 10, 2020, Nanjing University Chen Xi/Zhu Jingning/Zhang Chenyu published a research paper titled: Sperm microRNAs confer depression susceptibility to offspring in the Science Advances magazine, revealing that sperm microRNAs mediate depression traits in fathers To a new mechanism of inheritance between offspring.

MicroRNA (miRNA) is a type of endogenous small RNA with a length of about 20-24 nucleotides, which has a variety of important regulatory effects in cells.

First of all, in order to prove whether there is intergenerational inheritance of depression, the authors constructed a chronic mild stress (CMS) male depression mouse model (F0 generation), which was mated with normal female mice to obtain offspring mice (F1 generation) . Interestingly, when the normal group and the depression F1 generation mice were tested in the resting state, it was found that there was no significant difference in behavior; after being given mild stress, the depression F1 generation mice showed obvious performance compared to the normal F1 generation mice Depression-like behavior characteristics. The author further proved the depression susceptibility characteristics of F1 generation mice in the depression group by means of electrophysiology, immunofluorescence, and molecular level. These results indicate that depressive traits can indeed be passed on to offspring through intergenerational inheritance.

Furthermore, the authors found through sequencing that the sperm small RNA profile (15-50nt) of mice in the depression group changed significantly compared to normal mice. Among them, the miRNA changes were the most significant. The sperm small RNA or up-regulated miRNA of the depression group was microinjected After being injected into the fertilized eggs of normal mice, the offspring have a significant depression susceptibility phenotype. Neutralization of highly expressed miRNAs in fertilized eggs now improves depression susceptibility symptoms in the offspring of the depression group. These results indicate that it is indeed sperm small RNAs, especially miRNAs, that directly mediate the occurrence of intergenerational genetic phenomena in depression.

Finally, in the mechanism research, based on the results of single-cell sequencing, it was found that genes related to synaptic signaling, neuron differentiation, neurogenesis and other functions in early embryos have undergone significant changes. Bioinformatics predictions combined with in vitro experiments proved that depression in sperm is upregulated The miRNA can significantly inhibit the expression of key genes in these pathways.

Based on this, this reveals the molecular mechanism by which miRNAs in sperm may modulate genes related to nervous system development in early embryos to cause depression susceptibility symptoms in adult offspring.

In summary, the research team found that there is intergenerational genetic phenomenon in depression, which is of great significance for explaining the molecular mechanism of depression, and also provides a new perspective for studying the genetic law of mental diseases; elucidating miRNA-mediated depression in sperm The intergenerational genetic process and molecular mechanisms have enriched people’s understanding of the biological functions of miRNAs, helping us to better understand the laws of miRNAs as mediators in the transmission of genetic information, and have the potential to produce new drugs for the treatment of depression in the future Targets and treatment methods.

(source:internet, reference only)

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