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The cellular secret of how memories are made, and lost
Summary:
Scientists use a peptide to strengthen connections between brain cells and restore memory in a pre-clinical model.
Research led at The Hospital for Sick Children (SickKids) is illuminating the mechanism underlying memory, which could result in future therapeutic targets for conditions such as Alzheimer’s disease and dementia.
Alzheimer’s disease is a condition that causes memory loss, characterized by the accumulation of a protein, called A-beta, in the brain that damages neurons and their connections.
Published in Nature Neuroscience, Drs. Paul Frankland and Sheena Josselyn, Senior Scientists in the Neurosciences & Mental Health program, used a peptide to block adverse effects of the accumulation of A-beta in pre-clinical models – a technique that showed promise in restoring memory.
“This is the first step to developing targeted and effective future treatments for the restoration of memory in Alzheimer’s disease and dementia,” Josselyn says.
Peptide restores memory loss in pre-clinical model
In a pre-clinical model, the research team compared memory function in a model that expressed some of the same genes known to be one cause of Alzheimer’s disease with a control group. Using miniature microscopes developed at SickKids, the team captured real-time videos of neural activity in the hippocampus, a brain region crucial for memory formation and retrieval.
When memory was activated, the model with high levels of A-beta protein showed disrupted memory and a lack of coordinated brain cell activity when compared to the control group.
The research team gave the model with high A-beta a peptide which facilitates connections between brain cells by creating new contact points on neurons. After receiving the peptide, the synaptic connections between brain cells were strengthened, there was improved coordinated brain cell activity and regular memory function returned.
“Our work is providing a previously missing link in memory research.”
— Dr. Sheena Josselyn
Pictured above: A portion of a brain cell called a dendrite that receives information from other brain cells. The dots along the longer line are dendritic spines, areas where synaptic connections occur. Dendritic spines are decreased in people with Alzheimer’s disease. A SickKids research team has shown that a peptide can restore dendritic spines in a pre-clinical model.
Mechanism could inform future therapies to restore memory
The study is the first to connect receptors, higher-order neuronal dynamics and memory behavior in memory research.
“When we think of Alzheimer’s disease, we think of it as a disease of old age, but we don’t know yet when these changes in the brain start happening. Understanding the underlying mechanism could help us diagnose memory-related conditions faster and ultimately lead to new therapies,” Josselyn says.
These findings confirm the team’s previous research in The Proceedings of the National Academy of Sciences (PNAS) that showed poor memory was linked to deficits in structures that neurons use to communicate, and Frankland and Josselyn will continue their endeavors to demystify memory function and explore potential therapies based on this peptide.
This research was supported by the National Institute of Mental Health (NIMH), the Brain Canada Foundation, the Canadian Institutes of Health Research (CIHR) and the National Institutes of Health (NIH).