Memory Transferred Through Snails Using RNA Injection

Memory is one of the most important aspects of creatures with higher intelligence, and it was recently found that animals can mentally replay past events. Altering the processes that control memory could be enormously useful — as in restoring positive memories — or enormously harmful — as in deleting memories of events that were vital to learning. That’s technology’s lack of a moral imperative though — the outcome depends on how it’s used.

UCLA biologists report they have transferred a memory from one marine snail to another, creating an artificial memory, by injecting RNA from one to another. This research could lead to new ways to lessen the trauma of painful memories with RNA and to restore lost memories.

“I think in the not-too-distant future, we could potentially use RNA to ameliorate the effects of Alzheimer’s disease or post-traumatic stress disorder,” said David Glanzman, senior author of the study and a UCLA professor of integrative biology and physiology and of neurobiology. The team’s research is published May 14 in eNeuro, the online journal of the Society for Neuroscience.

RNA, or ribonucleic acid, has been widely known as a cellular messenger that makes proteins and carries out DNA’s instructions to other parts of the cell. It is now understood to have other important functions besides protein coding, including regulation of a variety of cellular processes involved in development and disease.

The researchers gave mild electric shocks to the tails of a species of marine snail called Aplysia. The snails received five tail shocks, one every 20 minutes, and then five more 24 hours later. The shocks enhance the snail’s defensive withdrawal reflex, a response it displays for protection from potential harm. When the researchers subsequently tapped the snails, they found those that had been given the shocks displayed a defensive contraction that lasted an average of 50 seconds, a simple type of learning known as “sensitization.” Those that had not been given the shocks contracted for only about one second.

The life scientists extracted RNA from the nervous systems of marine snails that received the tail shocks the day after the second series of shocks, and also from marine snails that did not receive any shocks. Then the RNA from the first (sensitized) group was injected into seven marine snails that had not received any shocks, and the RNA from the second group was injected into a control group of seven other snails that also had not received any shocks.

Remarkably, the scientists found that the seven that received the RNA from snails that were given the shocks behaved as if they themselves had received the tail shocks: They displayed a defensive contraction that lasted an average of about 40 seconds.

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Scientists know more about the cell biology of this simple form of learning in this animal than any other form of learning in any other organism, Glanzman said. The cellular and molecular processes seem to be very similar between the marine snail and humans, even though the snail has about 20,000 neurons in its central nervous system and humans are thought to have about 100 billion.

In the future, Glanzman said, it is possible that RNA can be used to awaken and restore memories that have gone dormant in the early stages of Alzheimer’s disease. He and his colleagues published research in the journal eLife in 2014 indicating that lost memories can be restored.

First Evidence that Animals Can Mentally Replay Past Events Found

Many innovations and breakthroughs have been based on or inspired by better understandings of animals, such as understanding bats leading to sonar and understanding scorpion venom leading to the development of new medicines. Perhaps animals have different mental processes than humans to remember past events, but in any case, there’s likely benefits to this research still unseen.

Neuroscientists at Indiana University have reported the first evidence that non-human animals can mentally replay past events from memory. The discovery could help advance the development of new drugs to treat Alzheimer’s disease.

The study, led by IU professor Jonathon Crystal, appears today in the journal Current Biology.

“The reason we’re interested in animal memory isn’t only to understand animals, but rather to develop new models of memory that match up with the types of memory impaired in human diseases such as Alzheimer’s disease,” said Crystal, a professor in the IU Bloomington College of Arts and Sciences’ Department of Psychological and Brain Sciences and director of the IU Bloomington Program in Neuroscience.

Under the current paradigm, Crystal said most preclinical studies on potential new Alzheimer’s drugs examine how these compounds affect spatial memory, one of the easiest types of memory to assess in animals. But spatial memory is not the type of memory whose loss causes the most debilitating effects of Alzheimer’s disease.

“If your grandmother is suffering from Alzheimer’s, one of the most heartbreaking aspects of the disease is that she can’t remember what you told her about what’s happening in your life the last time you saw her,” said Danielle Panoz-Brown, an IU Ph.D. student who is the first author on the study. “We’re interested in episodic memory — and episodic memory replay — because it declines in Alzheimer’s disease, and in aging in general.”

Episodic memory is the ability to remember specific events. For example, if a person loses their car keys, they might try to recall every single step — or “episode” — in their trip from the car to their current location. The ability to replay these events in order is known as “episodic memory replay.” People wouldn’t be able to make sense of most scenarios if they couldn’t remember the order in which they occurred, Crystal said.

To assess animals’ ability to replay past events from memory, Crystal’s lab spent nearly a year working with 13 rats, which they trained to memorize a list of up to 12 different odors. The rats were placed inside an “arena” with different odors and rewarded when they identified the second-to-last odor or fourth-to-last odor in the list.

The team changed the number of odors in the list prior to each test to confirm the odors were identified based upon their position in the list, not by scent alone, proving the animals were relying on their ability to recall the whole list in order. Arenas with different patterns were used to communicate to the rats which of the two options was sought.

After their training, Crystal said, the animals successfully completed their task about 87 percent of the time across all trials. The results are strong evidence the animals were employing episodic memory replay.

Additional experiments confirmed the rats’ memories were long-lasting and resistant to “interference” from other memories, both hallmarks of episodic memory. They also ran tests that temporarily suppressed activity in the hippocampus — the site of episodic memory — to confirm the rats were using this part of their brain to perform their tasks.

Crystal said the need to find reliable ways to test episodic memory replay in rats is urgent since new genetic tools are enabling scientists to create rats with neurological conditions similar to Alzheimer’s disease. Until recently, only mice were available with the genetic modifications needed to study the effect of new drugs on these symptoms.

“We’re really trying push the boundaries of animal models of memory to something that’s increasingly similar to how these memories work in people,” he said. “If we want to eliminate Alzheimer’s disease, we really need to make sure we’re trying to protect the right type of memory.”

Alzheimer’s Reversed in Mouse Model

It’s certainly a promising development in this area.

A team of researchers from the Cleveland Clinic Lerner Research Institute have found that gradually depleting an enzyme called BACE1 completely reverses the formation of amyloid plaques in the brains of mice with Alzheimer’s disease, thereby improving the animals’ cognitive function. The study, which will be published February 14 in the Journal of Experimental Medicine, raises hopes that drugs targeting this enzyme will be able to successfully treat Alzheimer’s disease in humans.

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“To our knowledge, this is the first observation of such a dramatic reversal of amyloid deposition in any study of Alzheimer’s disease mouse models,” says Yan, who will be moving to become chair of the department of neuroscience at the University of Connecticut this spring.

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“Our study provides genetic evidence that preformed amyloid deposition can be completely reversed after sequential and increased deletion of BACE1 in the adult,” says Yan. “Our data show that BACE1 inhibitors have the potential to treat Alzheimer’s disease patients without unwanted toxicity. Future studies should develop strategies to minimize the synaptic impairments arising from significant inhibition of BACE1 to achieve maximal and optimal benefits for Alzheimer’s patients.”

New Blood Test to Detect Alzheimer’s Developed

The earlier Alzheimer’s is detected, the more effective treatment for it can be. This blood test is part of an encouraging new wave of medical detections that are disrupting the costly and/or invasive methods used previously.

Scientists have developed a new blood test where a tiny drop of blood could be enough to predict the onset of Alzheimer’s – and that would mean better care and preventative measures could be taken much earlier.

Key to the new method is detecting the presence of amyloid beta (Aβ) deposits (or plaques), generally thought to be one of the main drivers of Alzheimer’s. Until now, detecting these plaques has proved tricky, and impossible as far as a blood test goes.

Now, that could be about to change. Based on a study of 373 Australian and Japanese patients, amyloid beta build up was accurately predicted in more than 90 percent of cases using the new procedure.

“From a tiny blood sample, our method can measure several amyloid-related proteins, even though their concentration is extremely low,” says one of the team, Koichi Tanaka from the Shimadzu Corporation in Japan.

“We found that the ratio of these proteins was an accurate surrogate for brain amyloid burden.”

We’re still not sure exactly how Alzheimer’s starts and develops, but abnormal levels of amyloid beta and another protein called tau seem to play a big role. Crucially, these proteins start to congregate long before noticeable Alzheimer’s symptoms like memory loss appear – maybe as many as 20 or 30 years prior.

Costly brain scans or difficult spinal fluid extraction are currently used to measure amyloid beta levels, but the diagnosis of the disease often just relies on looking for the visible symptoms of Alzheimer’s, at which stage it’s well developed.

That’s why a new early warning system, requiring just a small blood sample and giving several decades of warning, could be revolutionary.

The new process works using mass spectrometry to ionise and scan blood for a particular peptide or amino acid compound thought to be linked to amyloid beta concentrations. While a lot more testing is required to verify the link, it’s a promising start.

While we don’t yet have a cure for Alzheimer’s, knowing it’s on the way could help prompt some lifestyle changes regarding sleep, diet, and exercise that might help reduce its impact.

What’s more, it would give researchers a useful shortlist of people suitable for clinical trials, giving us a faster route to an eventual cure.

“I can see in the future, five years from now, where people have a regular checkup every five years after age 55 or 60 to determine whether they are on the Alzheimer’s pathway or not,” lead researcher Colin Masters, from the University of Melbourne in Australia, told the Associated Press.

Other research teams are also working on blood tests to try and detect Alzheimer’s, but none have yet made it out of the laboratory – an indication of just how hard it is to identify and deal with this disease.

Still, it’s encouraging that progress is being made, progress that could affect millions: in the US alone, more than 5 million people live with Alzheimer’s, and it’s the sixth leading cause of death in the United States.

Let’s hope that this latest blood test proves to be suitable for widespread use within the next few years.

Additional research done recently: A brain pacemaker shows progress in slowing Alzheimer’s disease.

Curcumin Found to Improve Memory in Study of Those With Mild Memory Loss

Good research on countering age-related cognitive problems with a simple remedy of curcumin. This is especially important when pharmaceutical corporations such as Pfizer are doing less research on Alzheimer’s and dementia.

The sample size of this study may also be relatively small, but its methodology looks rigorous enough, and turmeric has already been found to have considerable health benefits.

Daily consumption of a certain form of curcumin — the substance that gives Indian curry its bright color — improved memory and mood in people with mild, age-related memory loss, according to the results of a study conducted by UCLA researchers.

The research, published online Jan. 19 in the American Journal of Geriatric Psychiatry, examined the effects of an easily absorbed curcumin supplement on memory performance in people without dementia, as well as curcumin’s potential impact on the microscopic plaques and tangles in the brains of people with Alzheimer’s disease.

Found in turmeric, curcumin has previously been shown to have anti-inflammatory and antioxidant properties in lab studies. It also has been suggested as a possible reason that senior citizens in India, where curcumin is a dietary staple, have a lower prevalence of Alzheimer’s disease and better cognitive performance.

“Exactly how curcumin exerts its effects is not certain, but it may be due to its ability to reduce brain inflammation, which has been linked to both Alzheimer’s disease and major depression,” said Dr. Gary Small, director of geriatric psychiatry at UCLA’s Longevity Center and of the geriatric psychiatry division at the Semel Institute for Neuroscience and Human Behavior at UCLA, and the study’s first author.

The double-blind, placebo-controlled study involved 40 adults between the ages of 50 and 90 years who had mild memory complaints. Participants were randomly assigned to receive either a placebo or 90 milligrams of curcumin twice daily for 18 months.

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The people who took curcumin experienced significant improvements in their memory and attention abilities, while the subjects who received placebo did not, Small said. In memory tests, the people taking curcumin improved by 28 percent over the 18 months. Those taking curcumin also had mild improvements in mood, and their brain PET scans showed significantly less amyloid and tau signals in the amygdala and hypothalamus than those who took placebos.

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The researchers plan to conduct a follow-up study with a larger number of people. That study will include some people with mild depression so the scientists can explore whether curcumin also has antidepressant effects. The larger sample also would allow them to analyze whether curcumin’s memory-enhancing effects vary according to people’s genetic risk for Alzheimer’s, their age or the extent of their cognitive problems.

“These results suggest that taking this relatively safe form of curcumin could provide meaningful cognitive benefits over the years,” said Small, UCLA’s Parlow-Solomon Professor on Aging.

Diabetes Drug Significantly Reverses Alzheimer’s Memory Loss in Mice

It looks as though this may be a promising development in Alzheimer’s research.

A drug developed for diabetes could be used to treat Alzheimer’s after scientists found it “significantly reversed memory loss” in mice through a triple method of action.

The research, published in Brain Research, could bring substantial improvements in the treatment of Alzheimer’s disease through the use of a drug originally created to treat type 2 diabetes.

Lead researcher Professor Christian Holscher of Lancaster University in the UK said the novel treatment “holds clear promise of being developed into a new treatment for chronic neurodegenerative disorders such as Alzheimer’s disease.”

Research Finds Where the Earliest Signs of Alzheimer’s Occur in the Brain

This discovery has considerable potential for stopping the devastation Alzheimer’s often induces in those who develop the disease.

Researchers at Lund University in Sweden have for the first time convincingly shown where in the brain the earliest signs of Alzheimer’s occur. The discovery could potentially become significant to future Alzheimer’s research while contributing to improved diagnostics.

In Alzheimer’s, the initial changes in the brain occur through retention of the protein, ?-amyloid (beta-amyloid). The process begins 10-20 years before the first symptoms become noticeable in the patient.

In Nature Communications, a research team headed by Professor Oskar Hansson at Lund University has now presented results showing where in the brain the initial accumulation of ?-amyloid occurs. It is in the inner parts of the brain, within one of the brain’s most important functional networks — known as the default mode network.

“A big piece of the puzzle in Alzheimer’s research is now falling into place. We previously did not know where in the brain the earliest stages of the disease could be detected. We now know which parts of the brain are to be studied to eventually explain why the disease occurs,” says Sebastian Palmqvist, associate professor at Lund University and physician at Skåne University Hospital.

The default mode network is one of several networks, each of which has a different function in the brain. It is most active when we are in an awake quiescent state without interacting with the outside world, for example, when daydreaming. The network belongs to the more advanced part of the brain. Among other things, it processes and links information from lower systems.

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The difficulty of determining which individuals are at risk of developing dementia later in life, in order to subsequently monitor them in research studies, has been an obstacle in the research world. The research team at Lund University has therefore developed a unique method to identify, at an early stage, which individuals begin to accumulate ?-amyloid and are at risk.

The method combines cerebrospinal fluid test results with PET scan brain imaging. This provides valuable information about the brain’s tendency to accumulate ?-amyloid.

In addition to serving as a roadmap for future research studies of Alzheimer’s disease, the new results also have a clinical benefit:

“Now that we know where Alzheimer’s disease begins, we can improve the diagnostics by focusing more clearly on these parts of the brain, for example in medical imaging examinations with a PET camera,” says Oskar Hansson, professor at Lund University, and medical consultant at Skåne University Hospital.

Although the first symptoms of Alzheimer’s become noticeable to others much later, the current study shows that the brain’s communication activity changes in connection with the early retention of ?-amyloid. How, and with what consequences, will be examined by the research team in further studies.