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Friday, January 14, 2011

How DYRK1A Affects the Brain and Memory

The last blog involved the specific way DYRK1A worked. Now let's look at how it affects the brain and memory. Here are the 3 big ways that research has discovered to date. Remember, researchers keep adding details every year.

The first way DYRK1A affects the brain is from the beginning it is involved in the development of the brain. Specifically, it affects the normal brain volume.

The second affect is disrupting synaptic plasticity. Synaptic plasticity is the ability of the connection, or synapse, between two nerves to change. This connection strengthens and weakens as things are learned and forgotten.

The third big category that DYRK1A affects is memory consolidation. Memory consolidation is a process that stabilizes a memory trace after the initial acquisition.
This gene is turning out to be super-duper important! Let's explore the first piece of brain development.

"DYRK1A is a major player in both cell cycle regulation and synaptic plasticity. DYRK1A levels in the brains of DS subjects with free trisomy were found approximately 1.5-fold higher than those in normal subjects indicating that this protein is overproduced in a gene dosage-dependent manner in Down syndrome."   Guedj F et al.

Since it is involved in cell growth and reproduction, it is essential during development. In other words, having the correct dose of DYRK1A is an integral part of brain growth. At 1.5 times the amount, cell growth is disrupted, thereby, leading to low brain volume.

Is there anything we can do about the DYRK1A? Lucky for us, there are many studies looking at this problem.

There is one study published in 2009 called 'Green tea polyphenols rescue of brain defects induced by overexpression of DYRK1A.

I love the word 'rescue.'

PLoS One. 2009;4(2):e4606. Epub 2009 Feb 26.

'Green tea polyphenols rescue of brain defects induced by overexpression of DYRK1A.'

Guedj F, Sébrié C, Rivals I, Ledru A, Paly E, Bizot JC, Smith D, Rubin E, Gillet B, Arbones M, Delabar JM.

Functional and Adaptive Biology, Université Paris Diderot-Paris7 and CNRS, Paris, France.

The complete study is free online. Here is the link:

But in essence they reversed or as they put it rescued, brain volume, learning deficits and synaptic plasticity feeding the transgenic mice green tea polyphenols. Transgenic mice have been genetically altered from the wild type mice or normal mouse.

"We investigated the possibility of correcting these phenotypes through modulation of DYRK1A activity. EGCG can cross the blood-brain barrier and the placental barrier. EGCG is the major catechin in green tea leaves (40 to 50% of the total catechins amount). Indeed, feeding a green tea drink to mice (usually drinking 3–5 ml/day) is equivalent to administering 0.6 mg/day pure EGCG."

Green tea reduces the activity of DYRK1A. In essence returning the gene expression to a more normal amount.

They fed mice a green tea drink from gestation (started during initial mating period) to adulthood and saw positive results. Using MRI technology the researchers measured brain volume.

To test learning deficits, researchers use what is called a novel object recognition test. This test is where the mice are trained with 2 objects and then one of the objects is changed to a new object. Mice should spend most of their time checking out the new object and less time with the familiar object.

The results were significant. The transgenic mice fed the green tea had no learning deficit while the transgenic mice fed only water had close to zero memory capabilities.

Tomorrow........the burning question...what is synaptic plasticity? And why is it important?

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