Decreased cell number in the cerebellum

It has been known for some time that there is a decreased number of cells in parts of the brain of individuals with DS. A recent study has confirmed this decrease in embryos. In the brain region responsible for involuntary movements and fine motor coordination - the cerebellum - researchers in Italy have show that there is a reduction in the number of new cells born. There was no change in the number of cells dying (which is also a natural developmental process in some situations). The decrease in cells in the cerebellum is thought to contribute to the decrease in motor coordination seen in some individuals with DS.
Find the article here
Randal

Inhibition signalling in the brain

Recent studies have suggested that the major functional defect in a mouse model of DS may be an imbalance between excitation and inhibition brain signalling. This kind of imbalance is often seen to result in epilepsy. In a study by US researchers, the role of two DS genes was investigated. Here they found that by restoring the level of expression of these two genes to normal in the DS mouse, they could then restore the signalling imbalance. However, restoring the level of gene expression occurred from egg fertilisation and occurred throughout embryonic development, meaning that human gene therapy in young or adult individuals with DS may not produce an effect as great. Also, despite there being obvious brain changes in individuals with DS, there is substantial lack of evidence that the same brain signalling imbalance is occurring, as seen in the mouse model.
Additional commentary by the journal was made here
Randal

Reduced cell proliferation

One of the changes in the brain of individuals with DS is a decreased brain size. Evidence exists that this is may due to a reduction in the production of new cells during early development. One of the genes in three copies present in DS is Dyrk1a. Over the last 10 years evidence has been mounting suggesting that Dyrk1a is responsible for many cell functions including cell proliferation. This was recently tested and confirmed in cell lines, a mouse expressing too much of Dyrk1a and human embryonic stem cells. The Dyrk1a gene therefore presents a possible target for therapeutic intervention of decreased brain size in individuals with DS. Having enough brain cells present may then assist the brain to arrange itself properly and contribute to better brain function.
Find the article here
Find a review of Dyrk1a function here

Anti-depressants as therapies for DS

Researchers in Italy have used an anti-depressant to restore the behaviour deficits of a mouse with DS. Researchers also found that drug treatment prevented loss of neurons. Until now, no study has explored the possibility of pharmacologically improving cell maturation defects in DS during critical periods of brain development. The anti-depressant used was fluoxetine - or Prozac. Fluoxetine blocks the reuptake of a chemical neurotransmitter 5HT into cells, by forcing the 5HT to remain outside the cell, it is more likely to activate neighbouring cells and improve communication between them. DS is not typically associated with depression. However, fluoxetine can act by other mechanisms in different situations. In DS, where brain stem cells are lacking, fluoxetine can increase the production of these. The other exciting aspect of this discovery is that fluoxetine is already approved by drug administration agencies around the world for use in humans. While it's use in infants is not wide spread, clinical testing here is sure to advance.

Read the article here.

Randal

Human Down syndrome genes in stem cells

Researchers in Europe have created a stem cell bank in which each type of cell contains a copy of the human DS genes. The stem cells are from the mouse, which make it easier to study key developmental processes. Therefore, in addition to containing the mouse genes, the stem cell contains an extra human DS gene. One of the important findings from this study was that in addition to creating the cells they also tested for the gene's expression. Amongst the many genes they tested, not all were expressed in excess. The expression of the gene has a big impact on protein expression and ultimately the symptoms experienced by individuals with DS. This finding means that the possible genes for therapeutic targetting can be limited.

Read the study here.

Randal

A new mouse model of Down Syndrome

Researchers in the US and Canada have created a new mouse that is hoped will serve as a better model to understand some biological mechanisms leading to disabilities in DS. At present there are about half-a-dozen mouse models, however the new mouse is the first to express three copies of all of the mouse equivalents to the human genes. This is important because if a particular gene in three copies is responsible for a particular feature of DS then this can now be observed. Also, if one gene in three copies acts together with another gene in three copies then this can also be observed. Behaviour testing in these mice revealed they had learning problems. Events resulting from the disruption of so many genes as in DS is a complicated process, but at least, in a manner of speaking, we have now rounded up all the suspects.

Find the report here.

Randal

New home

Today marks the beginning of a new home for DSRA. I hope you find this blog incarnation more user friendly.

Randal