Chronic brain inflammation impairs two forms of long-term potentiation in the rat hippocampal CA1 area.
Neuroinflammation plays an important role in the progression of Alzheimer's disease (AD) and is characterized by the presence of activated microglia. We investigated whether chronic neuroinflammation affects the induction of N-methyl-d-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP) and NMDAR-independent LTP which is expressed by voltage-dependent calcium channel (VDCC). Chronic neuroinflammation was induced by administration of lipopolysaccharide (LPS) (28 days, 0.35 microg/h) to the fourth ventricle. The Morris water maze test was conducted to measure the memory impairment and then excitatory postsynaptic potentials were recorded extracelluarly from stratum radiatum in the rat hippocampal CA1 area to examine the changes in synaptic plasticity induced by LPS infusion. Chronic administration of LPS induced remarkable memory impairment. The field recording experiments revealed that the induction of both NMDAR-dependent LTP and NMDAR-independent LTP were impaired in the hippocampal Schaffer collateral-CA1 synapse in animals chronically infused with LPS. The present results show that chronic neuroinflammation can lead to the impaired spatial memory and attenuation of VDCC-dependent LTP as well as NMDAR-dependent LTP. The attenuation of synaptic plasticity may be caused by the impairment of both NMDAR and L-type Ca2+ via elevated levels of inflammatory proteins, which may underlie aspects of dementia.
Department of Physiology and Biophysics, Eulji University School of Medicine, Daejeon 301-832, South Korea.
Sun Seek
SS
Min
Hui Yan
HY
Quan
Jinhua
J
Ma
Jung-Soo
JS
Han
Byeong Hwa
BH
Jeon
Geun Hee
GH
Seol
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002908:Chronic Disease; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000503:physiopathology*; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000633:toxicity; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism
D015220:Calcium Channels; D008070:Lipopolysaccharides; D016194:Receptors, N-Methyl-D-Aspartate