Schematic of mice with dysfunctional and functional Wnt signaling Source: Alzheimer’s Research UK
Memory loss in mice has been reversed following the discovery of new information about a key mechanism underlying the loss of nerve connectivity in the brain. The team found Wnt proteins play a key role in the maintenance of nerve connectivity in the adult brain and could become targets for new treatments that prevent and restore brain function in neurodegenerative diseases.
Professor Salinas said: “Synapses are absolutely critical to everything that our brains do. When these important communication points are lost, nerve cells cannot exchange information and this leads to symptoms like memory and thinking problems. The Wnt pathway is emerging as a key player in the regulation of the formation, maintenance and function of synapses, and we have provided strong evidence that the Wnt proteins are also critical for memory. “Understanding the role of Wnts in Alzheimer’s disease is an important next step, as there is potential we could target this chain of events with drugs. Preventing or reversing the disruptions in connectivity and communication between nerve cells in Alzheimer’s would be a huge step forward.”
Increasing evidence suggests that deficiency in Wnt function contributes to disruption of brain connectivity in Alzheimer’s disease and therefore resulting in memory loss. The team studied the impact of a protein called Dkk1, known to block the action of Wnts and found at higher levels in people with Alzheimer’s, in brain circuits and memory.
Genetically modified mice in which Dkk1 can be switched on, disrupting the action of Wnts and its downstream chain of events were used. To avoid any disruption to normal brain development driven by Wnts and Dkk1, the researchers waited until the mice were adults before switching on Dkk1 in an area of the brain important for the formation of new memories.
When Dkk1 was switched on in the adult mice, the mice had memory problems, and this coincided with the presence of fewer synapses between nerve cells. However, when the researchers switched Dkk1 back off, the mice no longer had memory problems, the number of synapses increased back to normal levels and brain circuits were restored.
“This research sets a solid foundation for future work to explore the role of Wnts in diseases like Alzheimer’s, and this biological process is already a key target being explored by expert teams in the Alzheimer’s Research UK Drug Discovery Alliance. http://www.ucl.ac.uk/news/news-articles/0916/010916-brain-connectivity-memory
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