Scientists at the University of Warwick have provided the first evidence that the lack of a naturally occurring protein is linked to early signs of dementia.
Published in Nature Communications, the research found that the absence of the protein MK2/3 promotes structural and physiological changes to cells in the nervous system. These changes were shown to have a significant correlation with early signs of dementia, including restricted learning and memory formation capabilities.
An absence of MK2/3, in spite of the brain cells (neurons) having significant structural abnormalities, did not prevent memories being formed, but did prevent these memories from being altered.
The results have led the researchers to call for greater attention to be paid to studying MK2/3.
Lead researcher and author Dr Sonia Corrêa says that "Understanding how the brain functions from the sub-cellular to systems level is vital if we are to be able to develop ways to counteract changes that occur with aging.
"By demonstrating for the first time that the MK2/3 protein, which is essential for neuron communication, is required to fine-tune memory formation this study provides new insight into how molecular mechanisms regulate cognition."
Neurons can adapt memories and make them more relevant to current situations by changing the way they communicate with other cells.
Information in the brain is transferred between neurons at synapses using chemicals (neurotransmitters) released from one (presynaptic) neuron which then act on receptors in the next (postsynaptic) neuron in the chain.
MK2/3 regulates the shape of spines in properly functioning postsynaptic neurons. Postsynaptic neurons with MK2/3 feature wider, shorter spines than those without.
The researchers found that change, caused by MK2/3's absence, in the spine's shape restricts the ability of neurons to communicate with each other, leading to alterations in the ability to acquire new memories.
"Deterioration of brain function commonly occurs as we get older but, as result of dementia or other neurodegenerative diseases, it can occur earlier in people's lives," says Dr Corrêa. "For those who develop the early signs of dementia it becomes more difficult for them to adapt to changes in their life, including performing routine tasks.
"For example, washing the dishes; if you have washed them by hand your whole life and then buy a dishwasher it can be difficult for those people who are older or have dementia to acquire the new memories necessary to learn how to use the machine and mentally replace the old method of washing dishes with the new. The change in shape of the postsynaptic neuron due to absence of MK2/3 is strongly correlated with this inability to acquire the new memories."
Dr Corrêa argues that "Given their vital role in memory formation, MK2/3 pathways are important potential pharmaceutical targets for the treatment of cognitive deficits associated with aging and dementia."
- Katherine L. Eales, Oleg Palygin, Thomas O’Loughlin, Seyed Rasooli-Nejad, Matthias Gaestel, Jürgen Müller, Dawn R. Collins, Yuriy Pankratov, Sonia A.L. Corrêa. The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility. Nature Communications, 2014; 5: 4701 DOI: 10.1038/ncomms5701
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