Protective effects of lithium treatment for spatial memory deficits induced by tau hyperphosphorylation in splenectomized rats.
1. Postoperative cognitive dysfunction has become more prevalent in recent years. We used a splenectomized rat model with postoperative spatial learning and memory deficits to investigate the role of tau hyperphosphorylation and glycogen synthase kinase-3β (GSK-3β) within the hippocampus. 2. Cognitive function was assessed in a Y-maze 1 day before and 1, 3 and 7 days after surgery. We measured site-specific phosphorylation of hippocampal tau (Thr-205 and Ser-396), GSK-3β activity and expression of interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) mRNA and protein as markers of inflammation. We also tested the effects of treatment with lithium chloride (LiCl), a GSK-3β inhibitor. 3. Splenectomy was associated with learning and memory impairment 3 days later, as well as a rapid and massive hyperphosphorylation of hippocampal tau at Thr-205 and Ser-396, activated GSK-3β, and increased IL-1β and TNF-α expression. LiCl completely restored tau hyperphosphorylation to control levels. 4. These data from the splenectomized rat model suggest that inflammatory factors affect tau pathology through the GSK-3β signalling pathway and that LiCl is a promising treatment for postoperative cognitive deficits.
Tan
Wen-Fei
WF
Department of Anaesthesiology, First Hospital of China Medical University, Shenyang, China.
Cao
Xue-Zhao
XZ
Wang
Jun-Ke
JK
Lv
Huang-Wei
HW
Wu
Bin-Yang
BY
Ma
Hong
H
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000502:physiology; D000071679:Glycogen Synthase Kinase 3 beta; D018836:Inflammation Mediators / Q000378:metabolism / Q000627:therapeutic use; D018021:Lithium Chloride / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011183:Postoperative Complications / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013156:Splenectomy / Q000009:adverse effects*; D016896:Treatment Outcome; D016875:tau Proteins / Q000378:metabolism* / Q000502:physiology
D015415:Biomarkers; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D016875:tau Proteins; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride