Mouse model for epilepsy, Alzheimer's gives window into the working brain

August 21, 2014

University of Utah scientists have developed a genetically engineered line of mice that is expected to open the door to new research on epilepsy, Alzheimer's and other diseases.

The mice carry a protein marker, which changes in degree of fluorescence in response to different calcium levels. This will allow many cell types, including cells called astrocytes and microglia, to be studied in a new way.

"This is opening up the possibility to decipher how the works," said Petr Tvrdik, Ph.D., a research fellow in human genetics and a senior author on the study.

The research was published Aug. 14, 2014, in Neuron, a world-leading neuroscience journal. The work is the result of a three-year study involving multiple labs connected with The Brain Institute at the University of Utah. The lead author is J. Michael Gee, who is pursuing both a medical degree and a graduate degree in bioengineering at the university.

"We're really in the era of team science," said John White, Ph.D., professor of bioengineering, executive director of the Brain Institute and the study's corresponding author.

With the new mouse line, scientists can use a laser-based fluorescence microscope to study the calcium indicator in the of the living mouse, either when the mouse is anesthetized or awake. Calcium is studied because it is an important signaling molecule in the body and it can reveal how well the brain is functioning.

Using this method, the scientists are essentially creating a window into the working brain to study the interactions between neurons, astrocytes and microglia.

"We believe this will give us new insights for treatments of epilepsy and for new views of how the immune system of the brain works," White said.

About one-third of the 3 million Americans estimated to have epilepsy lack adequate treatment to manage the disease.

Describing a long-standing collaboration with fellow university researcher and professor of pharmacology and toxicology Karen Wilcox, Ph.D., White said, "We believe the glial cells are malfunctioning in . What we're trying to do is find out in what ways astrocytes participate in the disease."

This research is expected to lead to new classes of drugs.

The ability to track calcium changes in microglial cells will also open up the possibility of studying inflammatory diseases of the brain. Every neurological disease, including Multiple Sclerosis and Alzheimer's, appears to include components of inflammation, the scientists said.

"Live imaging and monitoring microglial activity and responses to inflammation was not possible before," said Tvrdik, particularly in living animals. In the past, researchers studied post-mortem tissue or relied on invasive approaches using synthetic dyes.

Explore further: Fight-or-flight chemical prepares cells to shift brain from subdued to alert

More information: "Imaging Activity in Neurons and Glia with a Polr2a-based and Cre-dependent GCaMP5G- IRES-tdTomato Reporter Mouse, Neuron, 2014.

Related Stories

Fight-or-flight chemical prepares cells to shift brain from subdued to alert

June 18, 2014
A new study from The Johns Hopkins University shows that the brain cells surrounding a mouse's neurons do much more than fill space. According to the researchers, the cells, called astrocytes because of their star-shaped ...

Memory relies on astrocytes, the brain's lesser known cells

July 28, 2014
When you're expecting something—like the meal you've ordered at a restaurant—or when something captures your interest, unique electrical rhythms sweep through your brain.

Immune response may cause harm in brain injuries, disorders

July 24, 2014
Could the body's own immune system play a role in memory impairment and cognitive dysfunction associated with conditions like chronic epilepsy, Alzheimer's dementia and concussions? Cleveland Clinic researchers believe so, ...

Researchers discover neuroprotective role of immune cell

July 22, 2014
A type of immune cell widely believed to exacerbate chronic adult brain diseases, such as Alzheimer's disease and multiple sclerosis (MS), can actually protect the brain from traumatic brain injury (TBI) and may slow the ...

New mapping approach lets scientists zoom in and out as the brain processes sound

July 31, 2014
Researchers at Johns Hopkins have mapped the sound-processing part of the mouse brain in a way that keeps both the proverbial forest and the trees in view. Their imaging technique allows zooming in and out on views of brain ...

Molecular imbalance linked to brain tumour seizures

July 14, 2014
Researchers in France may have discovered why some patients with a type of brain tumour have epileptic seizures.

Recommended for you

Cognitive cross-training enhances learning, study finds

July 25, 2017
Just as athletes cross-train to improve physical skills, those wanting to enhance cognitive skills can benefit from multiple ways of exercising the brain, according to a comprehensive new study from University of Illinois ...

Brain disease seen in most football players in large report

July 25, 2017
Research on 202 former football players found evidence of a brain disease linked to repeated head blows in nearly all of them, from athletes in the National Football League, college and even high school.

Lutein may counter cognitive aging, study finds

July 25, 2017
Spinach and kale are favorites of those looking to stay physically fit, but they also could keep consumers cognitively fit, according to a new study from University of Illinois researchers.

Zebrafish study reveals clues to healing spinal cord injuries

July 25, 2017
Fresh insights into how zebrafish repair their nerve connections could hold clues to new therapies for people with spinal cord injuries.

Brain stimulation may improve cognitive performance in people with schizophrenia

July 24, 2017
Brain stimulation could be used to treat cognitive deficits frequently associated with schizophrenia, according to a new study from King's College London.

New map may lead to drug development for complex brain disorders, researcher says

July 24, 2017
Just as parents are not the root of all their children's problems, a single gene mutation can't be blamed for complex brain disorders like autism, according to a Keck School of Medicine of USC neuroscientist.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.