Protective effects of lithium treatment for spatial memory deficits induced by tau hyperphosphorylation in splenectomized rats
Open Access
- 23 July 2010
- journal article
- research article
- Published by Wiley in Clinical and Experimental Pharmacology and Physiology
- Vol. 37 (10), 1010-1015
- https://doi.org/10.1111/j.1440-1681.2010.05433.x
Abstract
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.Keywords
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