Navigation Links
Scientists show how thinking can harm brain cells

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 excitotoxici ty 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 tri gger 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.


Source:University of Rochester Medical Center

Related biology news :

1. Scientists ID molecular switch in liver that triggers harmful effects of saturated and trans fats
2. Scientists Replicate Hepatitis C Virus in Laboratory
3. Scientists detect probable genetic cause of some Parkinsons disease cases
4. Scientists find missing enzyme for tuberculosis iron scavenging pathway
5. Scientists seek answers on what activates deadly anthrax spores
6. Yale Scientists Find MicroRNA Regulates Ras Cancer Gene
7. Scientists collaborate to assess health of global environment
8. Scientists decipher genome of fungus that can cause life-threatening infections
9. Scientists discover the cellular roots of graying hair
10. Scientists rid stem cell culture of key animal cells
11. Scientists develop new color-coded test for protein folding
Post Your Comments:

(Date:9/29/2015)... , Sept. 29, 2015  iDAvatars is excited to be ... its product to market. The official announcement was recently made ... event in San Francisco , where ... powered by IBM Watson. "It is both an ... 100 companies to bring to market the cognitive power of ...
(Date:9/28/2015)...  The monitoring of vital signs, such as ... an essential component of patient assessment. Changes in ... a patient,s condition. However, in general care areas ... during routine observation rounds only once every four ... these observation rounds, the warning signs can go ...
(Date:9/28/2015)... , September 28, 2015 According ... (Hardware & Software), Product (Scanner & Others), Application (Access ... Defense, & Others) & Geography Global - Forecast to ... to reach USD 3627.90 Million by 2020, at a ... Browse 65 market data T ables and ...
Breaking Biology News(10 mins):
(Date:10/12/2015)... ... 2015 , ... Dr. Carl Peck, MD, Chairman of NDA ... a Premier Expert consultant. NDA Partners Premier Experts are top tier consultants ... company's clients. Premier Experts collaborate to design and implement critical solutions to ...
(Date:10/11/2015)... ... October 11, 2015 , ... Intelligent Implant ... officially launched and multiple surgeries have been completed with this new posterior thoracolumbar ... Neuroscience & Spine Center of the Carolinas. The Revolution™ Spinal System pioneers ...
(Date:10/9/2015)... , Oct. 9, 2015 On October ... the Congressional Record her statement recognizing the third annual ... 11-17. IPAW is sponsored by the Plasma Protein ... is designed to:   , Raise global awareness ... plasma donors in saving and improving lives , ...
(Date:10/9/2015)...  DePuy Synthes Trauma* announced today the U.S. launch ... Technology**, the only pre-hydrated demineralized cancellous bone tissue matrix ... ankle, hand and wrist), including fusion, and for filling ... 2015 Orthopaedic Trauma Association (OTA) Annual Meeting. ... bone growth) and osteoinductive 2,3 (stimulates new bone ...
Breaking Biology Technology: