Protective effects of lithium treatment for spatial memory deficits induced by tau hyperphosphorylation in splenectomized rats

P>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-3 beta (GSK-3 beta) 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-3 beta activity and expression of interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha) mRNA and protein as markers of inflammation. We also tested the effects of treatment with lithium chloride (LiCl), a GSK-3 beta 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-3 beta, and increased IL-1 beta and TNF-alpha 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-3 beta signalling pathway and that LiCl is a promising treatment for postoperative cognitive deficits.