Recent studies have found a high genetic similarity of the psychiatric diseases schizophrenia and bipolar disorder, whose disease-specific changes in brain cells show an overlap of more than 70 percent. These changes affect gene expression, i.e., transcription of genes for the purpose of translation into functional proteins. A collaborative study now shows sex-specific biases in these changes, as well as in cellular control mechanisms based on endogenous short ribonucleic acid (RNA) chains.
The scientists identified an important role of microRNAs, a special group of these small RNA molecules, known for their extensive control of gene expression in all human cells. Targeting of a gene by one of these microRNAs can lead to a significant restriction of its expression. "The main problem is the enormous variety of possible combinations," says the lead author of the article published in the journal Cell Reports. "The human expresses about 2,500 of these microRNAs, and a single one can influence hundreds, maybe even thousands of genes."
For this reason, the researchers investigated gene expression in patient brains as well as human cultured nerve cells with a combination of RNA sequencing and bioinformatics. They found a difference in the expression of immune-related genes between men and women, especially with regard to cytokines, the messenger substances of immune cells. Upon exposition of the cultured male and female neuronal cells to some of these cytokines, the researchers found a transformation of nerve cells into to cholinergic neurons, defined by their use of the neurotransmitter "acetylcholine".
By sequencing the microRNAs at several time points during this process, the scientists were able to paint a detailed picture of the microRNA interface between the immune and neuronal systems. They identified the involvement of 17 partially sex-dependent families of microRNAs and generated an extensive network of 12,495 regulated genes. Using a multi-stage selection process, the most influential of these microRNA families were identified and confirmed in dedicated experiments. This led to the identification of the two sex-specifically expressed families mir-10 and mir-199 as interface between cytokines and cholinergic functions.
Psychiatric diseases are an important field for new therapeutic approaches because of their high genetic complexity and their inaccessibility to conventional forms of therapy. On the one hand, the current study demonstrates molecular parallels to the long-observed but previously unexplained clinical differences between disease-affected men and women. On the other hand, mechanisms on the basis of small RNA molecules could open up new avenues by influencing a large number of disease-relevant genes - a promising approach in the search for alternatives to traditional antipsychotic drugs. "Studies such as ours, which enable a comprehensive representation of microRNA interactions, are the first step on the path to developing new therapeutic substances," says the lead author.
https://aktuelles.uni-frankfurt.de/englisch/joint-study-shows-sex-specific-processes-in-schizophrenia-and-bipolar-disorder/
https://www.cell.com/cell-reports/fulltext/S2211-1247(19)31194-5
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fintegrative-transcriptom&filter=22
Sex specific micro RNAs link immune system and brain cells
- 1,193 views
- Added
Edited
Latest News
How protein synthesis in de…
By newseditor
Posted 22 Apr
Atlas of mRNA variants in d…
By newseditor
Posted 22 Apr
Mapping microbiome in metas…
By newseditor
Posted 22 Apr
Full-length mRNA packaged i…
By newseditor
Posted 22 Apr
Glucose-sensing mechanism t…
By newseditor
Posted 21 Apr
Other Top Stories
Exposure to chemical mixtures during pregnancy alters brain develop…
Read more
Making human brain stem cells grow for longer periods
Read more
A single transcription factor reprograms astrocytes in mouse striatum
Read more
Converting human stem cells to 8-cell totipotent embryo-like cells
Read more
AI and high content screening uncover hidden signatures of Parkinso…
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Long-term neuropsychologica…
By newseditor
Posted 23 Apr
Neuronal activity rapidly r…
By newseditor
Posted 22 Apr
A perspective on muscle phe…
By newseditor
Posted 22 Apr
Foxp1 suppresses cortical a…
By newseditor
Posted 22 Apr
Single-cell long-read seque…
By newseditor
Posted 22 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar