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
Source:University of Rochester Medical Center