Researchers on the Centre for Genomic Regulation (CRG) reveal that the Snhg11 gene is important for the operate and formation of neurons within the hippocampus. Experiments with mice and human tissues revealed the gene is much less lively in brains with Down syndrome, probably contributing to the reminiscence deficits noticed in individuals residing with the situation. The findings are revealed in the present day within the journal Molecular Psychiatry.
Historically, a lot of the main target in genomics has been on protein-coding genes, which in people constitutes round simply 2% of the whole genome. The remainder is “darkish matter,” together with huge stretches of non-coding DNA sequences that don’t produce proteins however are more and more acknowledged for his or her roles in regulating gene exercise, influencing genetic stability, and contributing to advanced traits and ailments.
Snhg11 is one gene discovered within the ‘darkish matter’. It’s a lengthy non-coding RNA, a particular kind of RNA molecule that’s transcribed from DNA however doesn’t encode for a protein. Non-coding RNAs are vital regulators of regular organic processes, and their irregular expression has been beforehand linked to the event of human ailments, corresponding to most cancers. The research is the primary proof {that a} non-coding RNA performs a important function within the pathogenesis of Down syndrome.
Down syndrome is a genetic dysfunction attributable to the presence of an additional copy of chromosome 21, often known as trisomy 21. It is the most typical genetic reason for mental incapacity, estimated to have an effect on 5 million individuals globally. Individuals with Down syndrome have reminiscence and studying issues, points beforehand linked to abnormalities within the hippocampus, part of the mind concerned in studying and reminiscence formation.
“The gene is especially lively within the dentate gyrus, part of the hippocampus essential for studying and reminiscence and one of many few mind areas the place new neurons are constantly created all through life. We discovered that abnormally expressed Snhg11 leads to decreased neurogenesis and altered plasticity, which performs a direct function in studying and reminiscence, thus indicating a key function within the pathophysiology of mental incapacity,” says Dr. César Sierra, first writer of the paper.
The authors studied the hippocampus in mouse fashions which have a genetic make-up much like Down syndrome in people. The hippocampus has many various cell sorts, and the research aimed to grasp how the presence of an additional chromosome 21 impacts these cells.
The researchers remoted nuclei from the mind cells and used a way referred to as single nucleus RNA sequencing to see which genes are lively in every cell. Some of the hanging findings had been in cells of the dentate gyrus, the place the researchers detected an vital discount of the expression of Snhg11. The researchers additionally discovered decrease ranges of Snhg11 in the identical sorts of tissues from human postmortem brains with trisomy 21, indicating the relevance for the human circumstances.
To grasp the consequences of the decreased Snhg11 expression on cognition and mind operate, the researchers then experimentally decreased the exercise of the gene within the brains of wholesome mice. They discovered that low ranges of Snhg11 had been ample to cut back synaptic plasticity, which is the power for neuronal connections to strengthen or weaken over time. Synaptic plasticity is essential for studying and reminiscence. It additionally decreased the mouse’s skill to create new neurons.
To grasp the real-world affect of their findings, the researchers additionally performed numerous behaviour assessments with mice. These experiments confirmed that low ranges of Snhg11 led to comparable reminiscence and studying issues as seen in Down syndrome, suggesting the gene regulates mind operate.
Snhg11 has beforehand been linked to cell proliferation in various kinds of most cancers. The researchers plan on finishing up additional analysis to find the precise mechanisms of motion concerned, data that might open potential avenues for brand new therapeutic interventions. They may even discover whether or not different genes involving lengthy non-coding RNAs, many that are but to be found, may also contribute to mental disabilities.
“There are various interventions to assist individuals with Down syndrome dwell independently, however solely few are pharmacological. Research like this assist lay the foundations to search out methods that may assist enhance reminiscence, consideration and language features, or forestall cognitive decline related to ageing,” says Dr. Mara Dierssen, co-author of the paper and Group Chief of the Mobile & Programs Neurobiology lab on the Centre for Genomic Regulation.
