Alzheimer's Disease is the most common neurodegenerative disorder in the United States -- affecting more than 5 million Americans. Perhaps the most devastating symptom of the disease is its characteristic loss of memory and identity, which can take a heavy psychological and emotional toll on its sufferers and their loved ones. But new research from scientists at UCLA's Brain Research Institute offers a glimmer of hope for patients in the early stages of Alzheimer's.
There may be a way for lost memories to be restored in the brain, according to the authors of the UCLA study, recently published online in the journal eLife.
The researchers suggest that long-term memory storage may not function as previously believed. The traditional view in neuroscience has held that memories are stored at the brain's synapses (the connecting points between neurons), which are destroyed by Alzheimer's disease. This causes the neurons to lose connection with one another in brain areas associated with memory, like the hippocampus. However, the UCLA researchers, led by integrative biologist/neurobiologist Dr. David Glanzman, found evidence, based on study of a sea snail, to suggest that long-term memory may not actually be stored at the synapses.
“That’s a radical idea, but that’s where the evidence leads," Glanzman said in a statement. "The nervous system appears to be able to regenerate lost synaptic connections. If you can restore the synaptic connections, the memory will come back. It won’t be easy, but I believe it’s possible.”
To better understand how learning and memory work, the research team studied the Aplysia, a marine snail. They studied a defensive response of the snail -- it withdraws its gill to protect it from possible harm -- and the neurons that give rise to this response. They chose the Aplysia specifically because it has very large neurons and far fewer neurons than other animals, making them easier to study, Glanzman told The Huffington Post.
The researchers administered several mild electric shocks to enhance the withdrawal response -- this response lasts for several days after the shocks, meaning that the snail had stored the response in its long-term memory. The shocks also caused serotonin, a feel-good hormone, to be released in the snail's nervous system.
Glanzman found long-term memory to be a function of the growth of new synaptic connection, caused by the release of serotonin in the nervous system. During the formation of long-term memories, the brain is creating new proteins that are involved in the creation of new synapses -- but if that process is interrupted, the proteins won't be synthesized and long-term memories won't be formed. However, if you inhibit the synthesis of proteins 24 hours after the memory is formed, the memory won't be disrupted.
"Once memories are formed, if you temporarily disrupt protein synthesis, it doesn’t affect long-term memory," Glanzman said. "That’s true in the Aplysia and in human’s brains.”
Studying the snail's neurons in a petri dish, the researchers found that even when memories disappeared, new synapses and new synaptic connections continued forming -- even when a protein-synthesis inhibitor was added 24 hours after the memory formation. But when they added a pulse of serotonin to the neurons, and then a protein-synthesis inhibitor immediately afterwards, both the synaptic growth and the memories were erased.
"This suggests that the 'reminder' pulse of serotonin triggered a new round of memory consolidation, and that inhibiting protein synthesis during this 'reconsolidation' erased the memory in the neurons," the study's press release noted.
When they repeated the experiment on the same snails and gave them shocks again, the erased memories returned -- synaptic connections that had been lost appeared to be restored. Because there was no clear pattern to which synapses remained and which were destroyed by the various interventions, the researchers hypothesized that memory is not stored in synapses.
"It is well known that in the early stages of Alzheimer’s disease there is significant destruction of synapses in the brain," Glanzman told The Huffington Post. "The amount of synaptic destruction roughly correlates with the severity of the memory loss. If you believe that memory is stored at synapses, then you would assume that when the synapses are gone, the memories that were mediated by those synaptic connections will be permanently lost. Our evidence indicates, however, that lost synapses can be restored, thereby restoring a specific long-term memory that appeared to be entirely eliminated."
Although the research is preliminary, the findings could have significant implications for the treatment of Alheimer's disease. If memory is not in the synapses, but instead is located elsewhere -- possibly the nucleus of the neurons -- then the destruction of synapses characteristic of Alzheimer's disease may not be what causes the loss of memories. In the early stages of the disease, before the neurons have begun dying, it may be possible to restore seemingly erased long-term memories.
“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,” Glanzman said.
If confirmed, the results could also have important applications for the treatment of Post-Traumatic Stress Disorder, the study's authors write.
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