Neuroinflammation and synaptic loss.
Neuroinflammation plays a critical role in the progression of many neurodegenerative, neuropsychiatric and viral diseases. In neuroinflammation, activated microglia and astrocytes release cytokines and chemokines as well as nitric oxide, which in turn activate many signal transduction pathways. The cytokines, interleukin-1 beta and tumor necrosis factor alpha, regulate transcription of a number of genes within the brain, which can lead to the formation of pro-inflammatory products of the arachidonic acid cascade. Formation of pro-inflammatory agents and associated cytotoxic products during neuroinflammation can be detrimental to neurons by altering synaptic proteins. Neuroinflammation as well as excitotoxic insults reduce synaptic markers such as synaptophysin and drebrin. Neurodegenerative, neuropsychiatric illnesses and viral infections are accompanied by loss of both pre- and post-synaptic proteins. These synaptic changes may contribute to the progressive cognitive decline and behavioral changes associated with these illnesses.
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bldg. 9, Rm. 1S126 MSC 0947, Bethesda, MD 20892-0947, USA. jrao@grc.nia.nih.gov
Jagadeesh S
JS
Rao
Matthew
M
Kellom
Hyung-Wook
HW
Kim
Stanley I
SI
Rapoport
Edmund A
EA
Reese
D000818:Animals; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009422:Nervous System Diseases / Q000378:metabolism / Q000473:pathology*; D013569:Synapses / Q000378:metabolism / Q000473:pathology*
D009419:Nerve Tissue Proteins