Nav: Home

Mechanism explains how seizures may lead to memory loss

October 16, 2017

Although it's been clear that seizures are linked to memory loss and other cognitive deficits in patients with Alzheimer's disease, how this happens has been puzzling. In a study published in the journal Nature Medicine, a team of researchers reveals a mechanism that can explain how even relatively infrequent seizures can lead to long-lasting cognitive deficits in animal models. A better understanding of this new mechanism may lead to future strategies to reduce cognitive deficits in Alzheimer's disease and other conditions associated with seizures, such as epilepsy.

"It's been hard to reconcile how infrequent seizures can lead to persistent changes in memory in patients with Alzheimer's disease," said corresponding author Dr. Jeannie Chin, assistant professor of neuroscience at Baylor College of Medicine. "To solve this puzzle, we worked with a mouse model of Alzheimer's disease focusing on the genetic changes that seizures might trigger in the memory center of the brain, the hippocampus, that could lead to loss of memory or other cognitive deficits."

The researchers measured the levels of a number of proteins involved in memory and learning and found that levels of the protein deltaFosB strikingly increase in the hippocampus of Alzheimer's disease mice that had seizures. DeltaFosB already is well known for its association with other neurological conditions linked to persistent brain activity of specific brain regions, such as addiction. In this study, the researchers found that after a seizure, the deltaFosB protein remains in the hippocampus for an unusually long time; its half-life - the time it takes for the amount of protein to decrease by half - is eight days. Most proteins have a half-life that is between hours and a day or two.

"Interestingly, because deltaFosB is a transcription factor, meaning that its job is to regulate the expression of other proteins, these findings led us to predict that the increased deltaFosB levels might be responsible for suppressing the production of proteins that are necessary for learning and memory," Chin said. "In fact, we found that when the levels of deltaFosB increase, those of other proteins, such as calbindin, decrease. Calbindin also has been known for a long time to be involved in Alzheimer's disease and epilepsy, but its mechanism of regulation was not known. We then hypothesized that deltaFosB might be regulating the production of calbindin."

Further investigations supported the researchers' hypothesis. The scientists showed that deltaFosB can bind to the gene calbindin suppressing the expression of the protein. When they either prevented deltaFosB activity or experimentally increased calbindin expression in the mice, calbindin levels were restored and the mice improved their memory. And when researchers experimentally increased deltaFosB levels in normal mice, calbindin expression was suppressed and the animals' memory deteriorated, demonstrating that deltaFosB and calbindin are key regulators of memory.

Connecting pieces of the puzzle

"Our findings have helped us answer the question of how even infrequent seizures can have such lasting detrimental effects on memory," Chin said. "We found that seizures can increase the levels of deltaFosB in the hippocampus, which results in a decrease in the levels of calbindin, a regulator of memory processes. DeltaFosB has a relatively long half-life, therefore even when seizures are infrequent, deltaFosB remains in the hippocampus for weeks acting like a brake, reducing the production of calbindin and other proteins, and disrupting the consequent brain activity involved in memory. The regulation of gene expression far outlasts the actual seizure event that triggered it."

The scientists found the same changes in deltaFosB and calbindin levels in the hippocampus of Alzheimer's disease patients and in the temporal lobe of epilepsy patients. However, they underscore that it is too soon to know whether regulating deltaFosB or calbindin could improve or prevent memory problems or other cognitive deficits in people with Alzheimer's disease. However, "now that we know that the levels of deltaFosB and calbindin are effective markers of brain activity in the hippocampus and memory function, we propose that these markers could potentially help assess clinical therapies for Alzheimer's and other diseases with seizures," Chin said.
-end-
Other contributors to this work include Jason C. You, Kavitha Muralidharan, Jin W. Park, Iraklis Petrof, Mark S. Pyfer, Brian F. Corbett, John J. LaFrancois, Yi Zheng, Xiaohong Zhang, Carrie A. Mohila, Daniel Yoshor, Robert A. Rissman, Eric J. Nestler and Helen E. Scharfman. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Thomas Jefferson University, New York University School of Medicine, Texas Children's Hospital, University of California San Diego School of Medicine, VA San Diego Healthcare System and Icahn School of Medicine at Mount Sinai.

This work was supported by the Margaret Q. Landenberger Research Foundation, the Hassel Family Foundation, and the National Institutes of Health Grants NS085171, F30-AG048710, NYS OMH, 193 AG051848, BX003040, AG0051839 and AG005131.

Baylor College of Medicine

Related Memory Articles:

Previously claimed memory boosting font 'Sans Forgetica' does not actually boost memory
It was previously claimed that the font Sans Forgetica could enhance people's memory for information, however researchers from the University of Warwick and the University of Waikato, New Zealand, have found after carrying out numerous experiments that the font does not enhance memory.
Memory boost with just one look
HRL Laboratories, LLC, researchers have published results showing that targeted transcranial electrical stimulation during slow-wave sleep can improve metamemories of specific episodes by 20% after only one viewing of the episode, compared to controls.
VR is not suited to visual memory?!
Toyohashi university of technology researcher and a research team at Tokyo Denki University have found that virtual reality (VR) may interfere with visual memory.
The genetic signature of memory
Despite their importance in memory, the human cortex and subcortex display a distinct collection of 'gene signatures.' The work recently published in eNeuro increases our understanding of how the brain creates memories and identifies potential genes for further investigation.
How long does memory last? For shape memory alloys, the longer the better
Scientists captured live action details of the phase transitions of shape memory alloys, giving them a better idea how to improve their properties for applications.
A NEAT discovery about memory
UAB researchers say over expression of NEAT1, an noncoding RNA, appears to diminish the ability of older brains to form memories.
Molecular memory can be used to increase the memory capacity of hard disks
Researchers at the University of Jyväskylä have taken part in an international British-Finnish-Chinese collaboration where the first molecule capable of remembering the direction of a magnetic above liquid nitrogen temperatures has been prepared and characterized.
Memory transferred between snails
Memories can be transferred between organisms by extracting ribonucleic acid (RNA) from a trained animal and injecting it into an untrained animal, as demonstrated in a study of sea snails published in eNeuro.
An immunological memory in the brain
Inflammatory reactions can change the brain's immune cells in the long term -- meaning that these cells have an 'immunological memory.' This memory may influence the progression of neurological disorders that occur later in life, and is therefore a previously unknown factor that could influence the severity of these diseases.
Anxiety can help your memory
Anxiety can help people to remember things, a study from the University of Waterloo has found.
More Memory News and Memory Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

TED Radio Wow-er
School's out, but many kids–and their parents–are still stuck at home. Let's keep learning together. Special guest Guy Raz joins Manoush for an hour packed with TED science lessons for everyone.
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.