Age-related memory loss is reversed in mice by increasing the plasticity of the brain

Memory loss has been successfully reversed in mice in a breakthrough study that could lead to treatments that prevent memory loss in humans.

Scientists at the University of Cambridge and the University of Leeds built their work off of recent evidence that shows perineuronal nets (PNNs) – cartilage-like structures that surround inhibitory neurons – play a role in the brain’s ability to learn and adapt.

PNNs contain compounds known as chondroitin sulfates, which include chondroitin 4-sulphate that inhibit the action of the neural networks and neuroplasticity (the brain’s ability to form and reorganize synaptic connections) and others like chondroitin 6-sulphate that promotes neuroplasticity.

The balance of these specific compounds change as humans age and when levels of chondroitin 6-sulphate decrease, so does a person’s ability to learn and form new memories changes – thus causing age-related memory loss. 

Knowing this, the team theorized whether manipulating the chondroitin sulfates composition of the PNNs might restore neuroplasticity and alleviate age-related memory deficits.

Their study consisted of treating aging mice with a virus capable of reconstructing the amount of 6-sulphate chondroitin sulfates to the PNNs and found that this completely restored memory in the older mice,  and to a level observed in younger mice.

This virus, or ‘viral vector’ could be the key to preventing memory loss in humans. 

Memory loss has been successfully reversed in mice in a breakthrough study that could lead to treatments that prevent memory loss in humans

Memory loss has been successfully reversed in mice in a breakthrough study that could lead to treatments that prevent memory loss in humans

Dr Jessica Kwok from the School of Biomedical Sciences at the University of Leeds said in a statement: ‘We saw remarkable results when we treated the aging mice with this treatment. 

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

Kwok and her colleagues used 20-month old mice (mice can live just months, but also years depending on the type and how long they are in captivity), which are considered to be very old, and conducted a number of visual and memory tests with them. 

One test observed if a mouse was able to recognize an object, with the researchers placing the specimen in a Y-shaped maze where the mouse was left to explore two identical objects at the end of the two arms. 

The  study treated aging mice with a virus capable of reconstructing the amount of 6-sulphate chondroitin sulfates to the PNNs and found that this completely restored memory in the older mice. The left image shows Wheat germ agglutinin (WGA), which binds to glycoproteins of the cell membrane, the middle image is the or the neurons found in the Perineuronal nets and the last image is the compounds after they have been manipulated

The  study treated aging mice with a virus capable of reconstructing the amount of 6-sulphate chondroitin sulfates to the PNNs and found that this completely restored memory in the older mice. The left image shows Wheat germ agglutinin (WGA), which binds to glycoproteins of the cell membrane, the middle image is the or the neurons found in the Perineuronal nets and the last image is the compounds after they have been manipulated

The mouse was removed from the maze, but placed back inside.

In this instance, one of the images was completely new and the other was the same as the mouse’s first experience. 

The researchers measured the amount of the time the mouse spent exploring each object to see whether it had remembered the object from the previous task, which showed older mice were less likely to remember the repeated image.

However, the aged mice recognized the repeated image after receiving the viral vector. 

Professor James Fawcett from the John van Geest Centre for Brain Repair at the University of Cambridge said in a statement: ‘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.’

With this successful work, the team was able to identified a potential drug for human use that can be taken by mouth and works in the same way as the viral vector – it inhibits the formations of PNNs. 

‘When this compound is given to mice and rats it can restore memory in ageing and also improves recovery in spinal cord injury,’ the scientists shared in a statement.

And the next step is to test the drug on animals with Alzheimer’s disease.

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