Scientists at the Centre for Genomic Regulation have actually found the important function of the Snhg11 gene in nerve cell function and formation in the hippocampus, connecting its minimized activity to memory deficits in Down syndrome. This study, which uses mouse designs and human tissue analysis, marks a considerable action in comprehending the hereditary basis of Down syndrome, focusing on the largely uncharted “dark matter” of the genome. The research study highlights the capacity of targeting long non-coding RNAs like Snhg11 for establishing new therapeutic interventions focused on enhancing cognitive functions in individuals with Down syndrome.The intellectual special needs observed in people with three copies of chromosome 21 might be associated to lowered activity of the Snhg11 gene in their brains.Scientists at the Centre for Genomic Regulation (CRG) have found the significant role of the Snhg11 gene in the advancement and performance of hippocampal neurons. Experiments including mice and human samples have shown lowered activity of this gene in Down syndrome-affected brains, suggesting a link to the memory challenges faced by people with the syndrome. The findings were just recently released in the journal Molecular Psychiatry.Traditionally, much of the focus in genomics has actually been on protein-coding genes, which in human beings constitutes around just 2% of the entire genome. The rest is “dark matter”, consisting of huge stretches of non-coding DNA series that do not produce proteins but are progressively acknowledged for their functions in controling gene activity, affecting hereditary stability, and contributing to complex traits and diseases.Snhg11 is one gene discovered in the dark matter. It is a long non-coding RNA, a special kind of RNA particle that is transcribed from DNA but does not encode for a protein. Non-coding RNAs are very important regulators of normal biological processes, and their irregular expression has actually been previously linked to the advancement of human diseases, such as cancer. The study is the very first proof that a non-coding RNA plays an important role in the pathogenesis of Down syndrome.Down Syndrome and Snhg11s RoleDown syndrome is a genetic disorder caused by the presence of an extra copy of chromosome 21, also referred to as trisomy 21. Its the most common hereditary cause of intellectual special needs, approximated to affect 5 million people globally. Individuals with Down syndrome have memory and knowing issues, problems formerly linked to abnormalities in the hippocampus, a part of the brain associated with learning and memory development.” The gene is particularly active in the dentate gyrus, a part of the hippocampus crucial for learning and memory and among the few brain regions where brand-new nerve cells are constantly created throughout life. We found that abnormally revealed Snhg11 lead to lowered neurogenesis and transformed plasticity, which plays a direct function in knowing and memory, thus indicating a key function in the pathophysiology of intellectual disability,” states Dr. César Sierra, first author of the paper.The authors studied the hippocampus in mouse designs which have a genetic makeup comparable to Down syndrome in human beings. The hippocampus has lots of different cell types, and the study intended to understand how the existence of an additional chromosome 21 affects these cells.The activity of Snhg11 (red) imagined in the dentate gyrus region of the hippocampus in mice. Credit: Cesar Sierra/Centro de Regulación Genómica (CRG) The scientists isolated nuclei from the brain cells and utilized a technique called single nucleus RNA sequencing to see which genes are active in each cell. One of the most striking findings remained in cells of the dentate gyrus, where the researchers spotted an important reduction of the expression of Snhg11. The scientists also discovered lower levels of Snhg11 in the exact same kinds of tissues from human postmortem brains with trisomy 21, indicating the importance for the human cases.To understand the effects of the lowered Snhg11 expression on cognition and brain function, the scientists then experimentally lowered the activity of the gene in the brains of healthy mice. They discovered that low levels of Snhg11 were sufficient to minimize synaptic plasticity, which is the capability for neuronal connections to enhance or damage gradually. Synaptic plasticity is vital for finding out and memory. It likewise minimized the mouses ability to develop brand-new neurons.Future Directions and Potential TherapiesTo understand the real-world impact of their findings, the scientists also carried out numerous behavior tests with mice. These experiments validated that low levels of Snhg11 resulted in similar memory and learning problems as seen in Down syndrome, recommending the gene regulates brain function.Snhg11 has formerly been linked to cell proliferation in different types of cancer. The researchers intend on performing even more research to discover the exact systems of action included, info that might open possible avenues for new healing interventions. They will also explore whether other genes including long non-coding RNAs, much of which are yet to be discovered, may likewise add to intellectual disabilities.” There are many interventions to help people with Down syndrome live independently, however only a few are pharmacological. Studies like this assistance lay the structures to discover methods that can assist improve memory, language, and attention functions, or prevent cognitive decrease connected with aging,” states Dr. Mara Dierssen, co-author of the paper and Group Leader of the Cellular & & Systems Neurobiology lab at the Centre for Genomic Regulation.Reference: “The lncRNA Snhg11, a brand-new prospect contributing to neurogenesis, plasticity, and memory deficits in Down syndrome” by Cesar Sierra, Miguel Sabariego-Navarro, Álvaro Fernández-Blanco, Sonia Cruciani, Alfonsa Zamora-Moratalla, Eva Maria Novoa and Mara Dierssen, 27 February 2024, Molecular Psychiatry.DOI: 10.1038/ s41380-024-02440-9.
Researchers at the Centre for Genomic Regulation have discovered the critical function of the Snhg11 gene in nerve cell function and development in the hippocampus, linking its decreased activity to memory deficits in Down syndrome. The research study highlights the capacity of targeting long non-coding RNAs like Snhg11 for developing brand-new healing interventions intended at improving cognitive functions in people with Down syndrome.The intellectual special needs observed in individuals with 3 copies of chromosome 21 may be attributed to minimized activity of the Snhg11 gene in their brains.Scientists at the Centre for Genomic Regulation (CRG) have actually found the substantial role of the Snhg11 gene in the development and performance of hippocampal neurons. The scientists likewise discovered lower levels of Snhg11 in the exact same types of tissues from human postmortem brains with trisomy 21, indicating the importance for the human cases.To understand the effects of the minimized Snhg11 expression on cognition and brain function, the scientists then experimentally reduced the activity of the gene in the brains of healthy mice. These experiments verified that low levels of Snhg11 led to comparable memory and learning problems as seen in Down syndrome, recommending the gene manages brain function.Snhg11 has previously been connected to cell expansion in various types of cancer.
