by Researchers at the Centre for Genomic Regulation (CRG) have made a significant discovery linking learning and memory problems in Down syndrome to alterations in the “dark matter” of the genome. The study, published in the journal Molecular Psychiatry, highlights the critical role of the Snhg11 gene in the formation and function of neurons in the hippocampus.
While the focus in genomics has traditionally been on protein-coding genes, only making up around 2% of the entire genome, the remaining “dark matter” includes non-coding DNA sequences that play essential roles in regulating gene activity and influencing genetic stability. Snhg11, a long non-coding RNA, is one such gene found in the dark matter, with abnormal expression linked to the development of diseases like cancer.
In individuals with Down syndrome, characterized by an extra copy of chromosome 21, the Snhg11 gene is less active in the brain, particularly in the dentate gyrus of the hippocampus. This reduction in gene activity results in decreased neurogenesis and altered plasticity, impacting learning and memory functions. The study provides the first evidence of a non-coding RNA’s critical role in the pathogenesis of Down syndrome and intellectual disability.
By studying mouse models with genetic similarities to Down syndrome and analyzing human postmortem brain tissues with trisomy 21, the researchers confirmed the significance of reduced Snhg11 expression in cognitive impairment. Experimental manipulation of Snhg11 activity in healthy mice revealed its direct impact on synaptic plasticity and neurogenesis, essential for memory formation.
The findings suggest that Snhg11 may play a crucial role in regulating brain function and could serve as a potential therapeutic target for addressing memory and learning deficits in Down syndrome. Further research will focus on unraveling the mechanisms of action of Snhg11 and exploring other long non-coding RNAs that may contribute to intellectual disabilities, paving the way for innovative interventions to improve cognitive functions in individuals with Down syndrome.
Dr. Mara Dierssen, co-author of the study, emphasizes the importance of such research in developing strategies to enhance memory, attention, and language functions in individuals with Down syndrome. While there are limited pharmacological interventions available, studies like this open doors for new therapeutic approaches to support independence and cognitive well-being in individuals with Down syndrome.
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1. Source: Coherent Market Insights, Public sources, Desk research
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