Most people have 46 chromosomes in each cell, divided into 23 pairs: people with Down syndrome (DS) have an extra copy of chromosome 21, wh...
Most people have 46 chromosomes in each cell, divided into 23 pairs: people with Down syndrome (DS) have an extra copy of chromosome 21, which carries more than 200 genes.
In this study, published in Cell Reports, UCL researchers, using the support of Cardiff University and the Francis Crick Institute, used mouse models to find out how these additional genes are found to cause learning problems.
Chromosome 21 and its genes can also be found in mice, although the genes were distributed across three different mouse chromosomes in three smaller regions. These are chromosomes 16, 10 and 17 of mice that contain 148 genes, 62 genes and 19 genes, respectively.
The researchers examined the effect of genes in each of these three different regions of mice (chromosomes) on learning and memory. To this end, three different strains of mice (groups of mice) were genetically engineered to carry an additional copy of one of the groups of genes on chromosomes 16, 10 or 17 of the mouse.
During the navigation tests, in which the mice had to go through a simple "left-right" T-maze, each group was measured both in terms of their memory and their ability to make decisions.
During these tests, the electrical activity of brain regions important for memory and decision-making was also monitored using an electroencephalogram (EEG).
The researchers found that one of the strains of mice (`` Dp10Yey '' mice) had poor memory and irregular cerebral blood flow (signals) in a part of the brain called the hippocampus, which was known to be very important to memory ,
They also discovered that another strain ("Dp1Tyb" mouse) had poor decision-making ability and a poor brain signal between the hippocampus and the prefrontal cortex, which is necessary for planning and decision-making. And the third strain ("Dp17Yey" mouse) had no unusual electrical activity in the brain.
Professor Matthew Walker, co-author at UCL's Queen Square Institute of Neurology, said: "These results are a complete surprise: we didn't expect the three different sets of genes to work completely differently."
"Scientists have traditionally assumed that a single gene or genes are the likely cause of the intellectual disabilities associated with Down syndrome.
"We have shown for the first time that different and multiple genes contribute to the various cognitive problems associated with Down syndrome."
The researchers will now find out specifically which genes are responsible for memory and decision disorders within smaller groups of genes.
Corresponding author Professor Elizabeth Fisher (Queen Square Institute of Neurology, UCL) said: "Our study provides essential information on the underlying mechanisms of neurological disability in Down syndrome and shows that intellectual disability in Down syndrome can be the result of various genetic disorders Be brains that underlie functional and regional abnormalities.
"This implies that therapies for people with Down syndrome should indicate multiple processes, and we have taken the first steps to identify some of these processes."
The researchers received support from Wellcome grants.
References : Chang, P., Bush, D., Schorge, S., Good, M., Canonica, T., Shing, N., Noy, S., Wiseman, FK, Burgess, N., Tybulewicz, VLJ, Walker, MC and Fisher, EMC (2020). Change in hippocampal prefrontal neuronal dynamics in mouse models with Down syndrome. Cell Reports, 30 (4), 1152-1163.e4. https://doi.org/10.1016/j.celrep.2019.12.065
This article has been republished from the following documents . Note: The material may have been changed in terms of length and content. Contact the specified source for more information.
