X-Message-Number: 27332
From: "Basie" <>
Subject: Scientists Show Thinking Can Harm Brain Cells
Date: Sat, 5 Nov 2005 16:53:13 -0500

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 --  
like the one shown above -- 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. 
(Image courtesy of National Institutes of Health)

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.

Basie http://www.agingtheory.com/pages/1/index.htm 

Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=27332