New Study Uncovers Direct Link Between Learning and Memory Impairment and Specific Gene

A gene previously associated with intellectual disability has been discovered to play a role in regulating learning and memory in mice.

The KDM5B gene has been connected to autism and a few disorders associated with intellectual disabilities in the past. Certain variations are also linked to decreased brain function in the general population, though not to the point where there is a noticeable impairment or behavioral symptoms.

Researchers from King’s College London, the University of Exeter, and the University of California, Irvine, have determined that decreased gene function in the brain leads to impaired learning and memory, along with a decline in the brain's capacity to enhance connections between neurons. This weakening of neuronal connections is crucial for memory formation.

The team's most recent mouse study, which was just published in the Journal of Neuroscience, details the reduced learning and memory capacities of mice that were bred without a fully functional KDM5B gene. The researchers also decreased the amount of this gene in the hippocampus, a part of the brain involved in memory, in a different group of adult mice in order to rule out the possibility that the effect may have been brought on by an effect on brain development.

They discovered that certain mice developed epileptic seizures as a result of decreased gene function and that their memory and learning also declined. It was suggested by laboratory experiments that there was less neuronal connection strengthening during memory formation.

Memory and the ability to learn are fundamental to our intellectual potential, yet we still have a lot to learn about the underpinning mechanisms. For more than a decade, the KDM5B gene has been linked to autism and some forms of intellectual disability, but a mutation in this gene alone is not always sufficient to cause these conditions, so it hasn’t been studied in detail. Our work shows that KDM5B is important for learning and memory and provides new insight into the fundamental mechanisms of memory and learning, which is crucial on the pathway to finding new ways to improve these functions.”

Albert Basson, Professor, University of Exeter

Professor Basson’s research group began the work at King’s College London.

KDM5B can alter the genetic material's structure in human cells, which controls the expression of genes required for brain function or development at the appropriate level and at the appropriate time.

We set out to investigate whether KDM5B’s ability to modify genetic material has a direct impact on learning and memory. We’ve discovered that the gene has a direct impact on learning and memory – which is distinct from any effect during brain development. This gene will now be of much greater interest to researchers on the quest for new treatments for conditions including autism, and other intellectual disability disorders.”

Dr. Leticia Peres-Sisquez, Researcher, King’s College London

Source:
Journal reference:

Pérez-Sisqués, L., et al. (2024) The Intellectual Disability Risk Gene Kdm5b Regulates Long-Term Memory Consolidation in the Hippocampus. Journal of Neuroscience. doi.org/10.1523/JNEUROSCI.1544-23.2024

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