Posts tagged aplysia
Articles and news from the latest research reports.
Neuroscientists use snail research to help explain “chemo brain”
It is estimated that as many as half of patients taking cancer drugs experience a decrease in mental sharpness. While there have been many theories, what causes “chemo brain” has eluded scientists.
In an effort to solve this mystery, neuroscientists at The University of Texas Health Science Center at Houston (UTHealth) conducted an experiment in an animal memory model and their results point to a possible explanation. Findings appeared in The Journal of Neuroscience.
In the study involving a sea snail that shares many of the same memory mechanisms as humans and a drug used to treat a variety of cancers, the scientists identified memory mechanisms blocked by the drug. Then, they were able to counteract or unblock the mechanisms by administering another agent.
“Our research has implications in the care of people given to cognitive deficits following drug treatment for cancer,” said John H. “Jack” Byrne, Ph.D., senior author, holder of the June and Virgil Waggoner Chair and chairman of the Department of Neurobiology and Anatomy at the UTHealth Medical School. “There is no satisfactory treatment at this time.”
While much work remains, Byrne, who runs the university’s Neuroscience Research Center, said understanding how these drugs impact the brain is an important first step in alleviating this condition characterized by forgetfulness, trouble concentrating and difficulty multitasking.
Byrne’s laboratory is known for its use of a large snail called Aplysia californica to further the understanding of the biochemical signaling among nerve cells (neurons). The snails have large neurons that relay information much like those in humans.
When Byrne’s team compared cell cultures taken from normal snails to those administered a dose of a cancer drug called doxorubicin, the investigators pinpointed a neuronal pathway that was no longer passing along information properly.
With the aid of an experimental drug, the scientists were able to reopen the pathway. Unfortunately, this drug would not be appropriate for humans, Byrne said. “We want to identify other drugs that can rescue these memory mechanisms,” he added.
The scientists confirmed their findings in tests on the nerve cells of rats.
“The big picture is to determine if this cancer drug acts in the same way in humans,” Byrne said.
A Gene Linked to Disease Found to Play a Critical Role in Normal Memory Development
It has been more than 20 years since scientists discovered that mutations in the gene huntingtin cause the devastating progressive neurological condition Huntington’s disease, which involves involuntary movements, emotional disturbance and cognitive impairment. Surprisingly little, however, has been known about the gene’s role in normal brain activity.
Now, a study from The Scripps Research Institute’s (TSRI’s) Florida campus and Columbia University shows it plays a critical role in long-term memory.
“We found that huntingtin expression levels are necessary for what is known as long-term synaptic plasticity—the ability of the synapses to grow and change—which is critical to the formation of long-term memory,” said TSRI Assistant Professor Sathyanarayanan V. Puthanveettil, who led the study with Nobel laureate Eric Kandel of Columbia University.
In the study, published recently by the journal PLOS ONE, the team identified an equivalent of the human huntingtin protein in the marine snail Aplysia, a widely used animal model in genetic studies, and found that, just like its human counterpart, the protein in Aplysia is widely expressed in neurons throughout the central nervous system.
Using cellular models, the scientists studied what is known as the sensory-to-motor neuron synapse of Aplysia—in this case, gill withdrawal, a defensive move that occurs when the animal is disturbed.
The study found that the expression of messenger RNAs of huntingtin—messenger RNAs are used to produce proteins from instructions coded in genes—is increased by serotonin, a neurotransmitter released during learning in Aplysia. After knocking down production of the huntingtin protein, neurons failed to function normally.
“During the learning, production of the huntingtin mRNAs is increased both in pre- and post-synaptic neurons—that is a new finding,” Puthanveettil said. “And if you block production of the protein either in pre- or post-synaptic neuron, you block formation of memory.”
The findings could have implications for the development of future treatments of Huntington’s disease. While the full biological functions of the huntingtin protein are not yet fully understood, the results caution against a therapeutic approach that attempts to eliminate the protein entirely.
Scientists Create Novel Approach to Find RNAs Involved in Long-term Memory Storage
Despite decades of research, relatively little is known about the identity of RNA molecules that are transported as part of the molecular process underpinning learning and memory.
Now, working together, scientists from the Florida campus of The Scripps Research Institute (TSRI), Columbia University and the University of Florida, Gainesville, have developed a novel strategy for isolating and characterizing a substantial number of RNAs transported from the cell-body of neuron (nerve cell) to the synapse, the small gap separating neurons that enables cell to cell communication.
Using this new method, the scientists were able to identify nearly 6,000 transcripts (RNA sequences) from the genome of Aplysia, a sea slug widely used in scientific investigation.
The scientists’ target is known as the synaptic transcriptome—roughly the complete set of RNA molecules transported from the neuronal cell body to the synapse.
In the study, published recently in the journal Proceedings of the National Academy of Sciences, the scientists focused on the RNA transport complexes that interact with the molecular motor kinesin; kinesin proteins move along filaments known as microtubules in the cell and carry various gene products during the early stage of memory storage.
While neurons use active transport mechanisms such as kinesin to deliver RNA cargos to synapses, once they arrive at their synaptic destination that service stops and is taken over by other, more localized mechanisms—in much the same way that a traveler’s bags gets handed off to the hotel doorman once the taxi has dropped them at the entrance.
The scientists identified thousands of these unique sequences of both coding and noncoding RNAs. As it turned out, several of these RNAs play key roles in the maintenance of synaptic function and growth.
The scientists also uncovered several antisense RNAs (paired duplicates that can inhibit gene expression), although what their function at the synapse might be remains unknown.
“Our analyses suggest that the transported RNAs are surprisingly diverse,” said Sathya Puthanveettil, a TSRI assistant professor who designed the study. “It also brings up an important question of why so many different RNAs are transported to synapses. One reason may be that they are stored there to be used later to help maintain long-term memories.”
The team’s new approach offers the advantage of avoiding the dissection of neuronal processes to identify synaptically localized RNAs by focusing on transport complexes instead, Puthanveettil said. This new approach should help in better understanding changes in localized RNAs and their role in local translation as molecular substrates, not only in memory storage, but also in a variety of other physiological conditions, including development.
“New protein synthesis is a prerequisite for maintaining long term memory,” he said, “but you don’t need this kind of transport forever, so it raises many questions that we want to answer. What molecules need to be synthesized to maintain memory? How long is this collection of RNAs stored? What localized mechanisms come into play for memory maintenance? ”
(Source: scripps.edu)
Scientists reverse memory loss in animal brain cells
Neuroscientists at The University of Texas Health Science Center at Houston (UTHealth) have taken a major step in their efforts to help people with memory loss tied to brain disorders such as Alzheimer’s disease.
Using sea snail nerve cells, the scientists reversed memory loss by determining when the cells were primed for learning. The scientists were able to help the cells compensate for memory loss by retraining them through the use of optimized training schedules. Findings of this proof-of-principle study appear in the April 17 issue of The Journal of Neuroscience.
“Although much works remains to be done, we have demonstrated the feasibility of our new strategy to help overcome memory deficits,” said John “Jack” Byrne, Ph.D., the study’s senior author, as well as director of the W.M. Keck Center for the Neurobiology of Learning and Memory and chairman of the Department of Neurobiology and Anatomy at the UTHealth Medical School.
This latest study builds on Byrne’s 2012 investigation that pioneered this memory enhancement strategy. The 2012 study showed a significant increase in long-term memory in healthy sea snails called Aplysia californica, an animal that has a simple nervous system, but with cells having properties similar to other more advanced species including humans.
Yili Zhang, Ph.D., the study’s co-lead author and a research scientist at the UTHealth Medical School, has developed a sophisticated mathematical model that can predict when the biochemical processes in the snail’s brain are primed for learning.
Her model is based on five training sessions scheduled at different time intervals ranging from 5 to 50 minutes. It can generate 10,000 different schedules and identify the schedule most attuned to optimum learning.
“The logical follow-up question was whether you could use the same strategy to overcome a deficit in memory,” Byrne said. “Memory is due to a change in the strength of the connections among neurons. In many diseases associated with memory deficits, the change is blocked.”
To test whether their strategy would help with memory loss, Rong-Yu Liu, Ph.D., co-lead author and senior research scientist at the UTHealth Medical School, simulated a brain disorder in a cell culture by taking sensory cells from the sea snails and blocking the activity of a gene that produces a memory protein. This resulted in a significant impairment in the strength of the neurons’ connections, which is responsible for long-term memory.
To mimic training sessions, cells were administered a chemical at intervals prescribed by the mathematical model. After five training sessions, which like the earlier study were at irregular intervals, the strength of the connections returned to near normal in the impaired cells.
“This methodology may apply to humans if we can identify the same biochemical processes in humans. Our results suggest a new strategy for treatments of cognitive impairment. Mathematical models might help design therapies that optimize the combination of training protocols with traditional drug treatments,” Byrne said.
He added, “Combining these two could enhance the effectiveness of the latter while compensating at least in part for any limitations or undesirable side effects of drugs. These two approaches are likely to be more effective together than separately and may have broad generalities in treating individuals with learning and memory deficits.”
(Image courtesy: UC Berkeley)