Scientists uncover potential to restore lost memories in patients with early Alzheimer's
Blocking protein synthesis stops synaptic growth, preventing long-term memory formation
To reach their findings, the researchers "trained" the Aplysias to remember a number of mild electric shocks applied to their tail. The team explains that the snails present a defensive response to the electric shocks - which involves the hormone serotonin being released into their central nervous system, encouraging the growth of synaptic connections involved in long-term memory - in order to protect their gills from damage. This defensive response lasts a few days, which the researchers say represents the snails' long-term memory.
The researchers then monitored the sensory and motor neurons that intercede the snails' defensive response in a Petri dish; the synaptic connections that were present in the snails' bodies reformed in the dish. According to Glanzman, while long-term memories are being created, the brain makes new proteins that play a part in creating new synapses. But disruption of this process - through concussion, for example - can prevent protein synthesis, stopping long-term memories from being created.
The team demonstrated this process in the Petri dish. On adding serotonin, they witnessed the development of new synaptic connections between the sensory and motor neurons. But adding a protein synthesis inhibitor straight after adding serotonin stopped the growth of new synaptic connections, which prevented the formation of long-term memories.
"If you train an animal on a task, inhibit its ability to produce proteins immediately after training, and then test it 24 hours later, the animal doesn't remember the training," explains Glanzman. But he notes that if you train an animal and inject a protein synthesis inhibitor into its brain after 24 hours, its long-term memory remains intact.
"In other words," he adds, "once memories are formed, if you temporarily disrupt protein synthesis, it doesn't affect long-term memory. That's true in the Aplysia and in human's brains."
'As long as the neurons are still alive, the memory will still be there'
The team wanted to investigate whether loss of synapses occurs alongside loss of memories. First, they counted the number of synapses present in the aforementioned Petri dish and introduced a protein synthesis inhibitor 24 hours later. Another 24 hours later, they counted the number of synapses in the dish again. They found that delayed introduction of a protein synthesis inhibitor did not appear to interrupt the formation of long-term memories; they witnessed the growth of new synapses, as well as stronger synaptic connections between sensory and motor neurons.
The researchers then introduced serotonin to a Petri dish of sensory and motor neurons. After 24 hours, they added an additional pulse of serotonin to the dish to remind the neurons of the original electric shock training. They introduced a protein synthesis inhibitor to the dish straight after.
This process, the team says, eliminated both synaptic growth and long-term memory formation. They found that the number of synapses in the dish was the same as the number of synapses present before the electric shock training. This, the researchers say, indicates that the addition of the "reminder" serotonin activated a new wave of memory consolidation, but that blocking protein synthesis during this process deleted memories from the brain cells.
On conducting this experiment in the snails before applying a number of electric shocks to their tails, they found that the long-term memory believed to be lost was recovered, suggesting that the synaptic connections in the snails were restored. Glanzman says their findings could offer hope to individuals with early-stage Alzheimer's, as long-term memories may be stored in the nucleus of the neurons rather than the synapses, which are usually damaged in such patients.
He adds: "As long as the neurons are still alive, the memory will still be there, which means you may be able to recover some of the lost memories in the early stages of Alzheimer's."
The team plans to further investigate the restoration of memories and regrowth of synapses in Aplysias. Earlier this year, Medical News Today reported on a study published in the Journal of Neuroscience, which detailed how memory and learning deficits were restored in the mouse models of Alzheimer's.
Honor Whiteman