Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Scientists show how thinking can harm brain cells


Preconditioning could prevent injury to dendrites in neurologic diseases

Scientists at the University of Rochester Medical Center have targeted a new culprit and method of attack on neurologic functions in diseases such as Alzheimer’s and dementia associated with HIV.

In an article in the Nov. 1 issue of The Journal of Clinical Investigation, the Rochester scientists describe a new mechanism by which brain cells can be damaged during chronic neurodegenerative diseases. When inflammation occurs in the brain, nerve impulses that are passed between cells during routine activities like learning and memory can become toxic. Instead of triggering the formation of memories, these impulses can inflict injury on neurons and disrupt neurologic function.

Understanding this mechanism could provide a new path for drugs to treat the diseases. Working in collaboration with researchers at the University of California at San Diego, the Rochester scientists propose a strategy of chemical preconditioning to induce adaptations in nerve cells that would enable the cells to better withstand toxic attacks, prevent injury, and preserve function.

"Preconditioning would allow the nervous system to experience stress and become more resistant to future encounters with stress and the damage it can trigger," said Harris A. Gelbard, M.D., professor of Neurology at the University of Rochester Medical Center and the research project’s principal investigator.

A long-standing villain in neurodegenerative disease has been glutamate, an amino acid that normally acts as a neurotransmitter. Excess glutamate, however, can overly excite neurons, causing damage and death – a process called excitotoxicity. Some drugs developed for the treatment of Alzheimer’s disease, for example, are designed to lower the production of glutamate or block its transmission to reduce excitotoxic injury.

"But just blocking glutamate doesn’t seem to work efficiently in neurodegenerative diseases with inflammation," said Gelbard. "We reconsidered how excitotoxicity actually damages the nervous system in a functional way."

The scientists focused on dendrites, the crooked branches of neurons that carry impulses toward the body of the nerve cell, and synapses, the places where impulses pass from neuron to neuron. Injury to dendrites – characterized by swelling or beading, loss of dendrite spines, and reduction in size – is seen in HIV-1-associated dementia and Alzheimer’s.

In laboratory studies, brain cells and slices were exposed to platelet-activating factor, or PAF, a compound that promotes inflammation and plays many roles in the brain. It can be produced by neurons and takes part in the working of synapses, including activity associated with learning and remembering. It also is produced by immune cells during inflammation. The amount of PAF in the brain increases dramatically in HIV-1-associated dementia and other neurodegenerative diseases.

"We found that disease makes dendrites more vulnerable to excitotoxicity," said Matthew J. Bellizzi, a researcher and student in the M.D./Ph.D. program at the Medical Center and corresponding author of the journal article. "We also found that damage to the dendrites may not require abnormal glutamate exposure."

The lab studies showed that elevated levels of PAF promoted beading on dendrites and injury to synapses following bursts of synaptic activity similar to those thought to be involved in learning and memory.

"This mechanism does not just apply to HIV," Gelbard said. "It applies to Alzheimer’s, multiple sclerosis, Parkinson’s and any neurodegenerative diseases that have synaptic dysfunction with inflammation, which is virtually all of them."

In lab studies, brain cells were treated with diazoxide, a drug investigated for use in ischemic heart disease and strokes. Pretreatment before exposure to PAF prevented dendritic beading and preserved synaptic functions, the studies showed.

"Stressing the cells with small amounts could trigger protective genes and induce adaptations that will make the dendrites more able to withstand insults," Bellizzi said.

Diazoxide is not the only drug that would work, and others might be better, the researchers said. Memantine, a drug that blocks glutamate receptors, is used in the treatment of Alzheimer’s. Chemical preconditioning could represent an alternate or complementary strategy.

"Preconditioning to protect the synapse is likely to be more important in the early and middle phases of neurodegenerative diseases than simply preserving the cell body," Gelbard said.

Michael Wentzel | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich

nachricht Researchers Discover New Anti-Cancer Protein
22.03.2018 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Researchers Discover New Anti-Cancer Protein

An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.

The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

Modular safety concept increases flexibility in plant conversion

22.03.2018 | Trade Fair News

New interactive map shows climate change everywhere in world

22.03.2018 | Earth Sciences

New technologies and computing power to help strengthen population data

22.03.2018 | Earth Sciences

Science & Research
Overview of more VideoLinks >>>