Alzheimers Research UK explain 'what is dementia?'

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Scientists from Cambridge and Leeds have made a ground-breaking discovery after successfully reversing age-related memory loss. The researchers say their discovery could lead to the development of treatments to help prevent memory loss in people as they age. Research was conducted on mice; however, the same mechanism could also be used in humans as molecules and structures in the human brain are the same as those found in rodents.

The study, which was published in Molecular Psychiatry, looked at changes in the extracellular matrix of the brain which led to loss of memory associated with ageing.

The researchers found a way to help reverse these changes using genetic treatments and believe it may be possible to prevent humans from developing memory loss in their later life.

By increasing levels of chondroitin 6-sulphate using the viral vector memory and plasticity levels were restored to levels similar to healthy mice.

The study looked at perineuronal nets (PNNs) which are chondroitin sulphate proteoglycan-containing structures on the neuronal surface that have been implicated in the control of neuroplasticity and memory.

Age-related reduction of chondroitin 6-sulphates (C6S) leads to PNNs becoming more inhibitory.

Researchers investigated how a manipulation of the chondroitin sulphate (CS) composition of the PNNs could restore neuroplasticity and alleviate memory deficits in aged mice. 

To do this, they looked at 20-month-old mice which are considered to be very old and by implementing a suite of tests it was shown the mice exhibited deficits in their memory compared to six-month old mice.

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An example of one of the tests used involved the mice’s ability to recognise an object.

The mouse was placed at the start of a Y-shaped maze and left to explore two identical objects at the end of the two arms.

After a short while, the mouse was again placed in the maze, however, this time one arm contained a new object while the other contained a copy of the repeated object.

The team then measured the amount of time the mouse spent exploring each object noting whether it had remembered the object from the previous task.

The older mice were much less likely to remember the object.

A ‘viral vector’ was used on the ageing mice which is a virus capable of reconstituting the amount of 6-sulphate chondroitin sulphates to the PNNS.

It was found that this completely restored memory in the older mice to a level similar to their younger counterparts.

Scientists noted that by restoring C6S levels in aged animals rescued the memory deficits and restored cortical long-term potentiation, suggesting a strategy to improve age-related memory impairment.

Dr Jessica Kwok from the School of Biomedical Sciences at the University of Leeds said of the discovery: “We saw remarkable results when we treated the ageing mice with this treatment.

“The memory and ability to learn were restored to levels they would not have seen since they were much younger.”

Professor James Fawcett from the John van Geest Centre for Brain Repair at the University of Cambridge added: “What is exciting about this is that although our study was only in mice, the same mechanism should operate in humans – the molecules and structures in the human brain are the same as those in rodents.

“This suggests that it may be possible to prevent humans from developing memory loss in old age.”
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