What is memory loss?
Memory loss is often one of the most feared consequences of aging. The severity of this forgetfulness can vary greatly to include a loss of cognitive function that may be clinically diagnosed as dementia. Older adults often report an increase in the frequency of memory lapses. Despite making everyday tasks more challenging, this form of memory loss is categorised as a normal part of the aging process.
The science behind age-related memory loss
Neuroplasticity refers to the brain’s ability to change throughout our lives. Connections within the brain may be formed, lost or even rewired. This adaptability forms a crucial part of memory formation. The control of adult neuroplasticity involves specialised extracellular matrix structures known as perineuronal nets (PNNs). These are composed of chondroitin sulfate proteoglycans and predominantly surround inhibitory neurons.
PNNs first appear at the end of the critical period of neurodevelopment. Their stability throughout adulthood is associated with the importance of increasing the brain’s efficiency. The resulting decreased plasticity arises from the PNN matrix becoming more inhibitory. This is because of an increase in the ratio of chondroitin 4-sulphate (C4S) to chondroitin 6-sulphate (C6S).
C6S was the focus of a recent study, published in Molecular Psychiatry, that explored the role of this compound in age-related neuroplasticity and memory. Changes in C6S concentrations during aging alter the structure of the brain extracellular matrix. This affects our ability to form new memories. The PNN’s chondroitin sulphate composition must remain balanced as any alterations, such as changes in the C4S/C6S ratio, are associated with memory decline.
How was memory function measured in the mice?
Several memory tests were used to determine the differences in mice memory function. These assessments also allowed the scientists to evaluate how differences in memory ability vary according to different brain regions. Older mice (20 months) scored lower on these tests confirming a decrease in memory efficiency with age. Changes in their performance could then be tracked to determine the effects of the subsequent treatment on their memory ability.
The use of genetic treatments to reverse this age-related memory loss
A viral vector was used to alter concentrations of chondroitin 6-sulphate in the PNNs. A lowering of C6S levels resulted in premature memory loss whereas restoration of C6S levels was linked to a significant improvement in memory ability. Mice that received the genetic treatment demonstrated an overall increase in neuroplasticity and a significant improvement in their memory function.
Can this treatment be applied to humans?
The ability of the treated older mice to perform nearly as well as some of the young mice on the memory tests has provided an example of rejuvenation. Despite many biological similarities, the complexity and intricacy of the human brain presents several limitations regarding the use of mouse models to study humans. However, the concept of viral vector treatment is something that currently applies to several human neurological conditions.
A potential drug for the treatment of age-related memory loss has already been identified. This drug, licensed for human use, works by inhibiting the formation of PNNs. This provides hope for the future treatment of age-related memory loss.
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*Disclaimer: This information is for educational purposes only.