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

Abstract

SUMMARY1. 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-3b (GSK-3b) 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-3b activity and expression of interleukin-1b (IL-1b), tumour necrosis factor-a (TNF-a) mRNA and protein as markers of inflammation. We also tested the effects of treatment with lithium chloride (LiCl), a GSK-3b 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-3b, and increased IL-1b and TNF-a 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-3b signalling pathway and that LiCl is a promising treatment for postoperative cognitive deficits.

Lithium modulates the production of peripheral and cerebral cytokines in an animal model of mania induced by dextroamphetamine

“…In the present study, Li treatment reversed the cytokine changes (IL‐4, IL‐6, IL‐10, and TNF‐α) induced by d‐AMPH in both the brain and serum of treated rats. It is well known that Li is an effective medication for the treatment of BD , and several studies suggest that Li exerts anti‐inflammatory effects [e.g., suppression of cyclooxygenase‐2 expression, inhibition of IL‐1β and TNF‐α production, and enhancement of IL‐2 and IL‐10 synthesis ]. However, some studies indicate that, under certain experimental conditions, Li also exhibits pro‐inflammatory properties [e.g., induction of the synthesis of IL‐4, IL‐6 and other pro‐inflammatory cytokines ].…”

Tau Protein Modifications and Interactions: Their Role in Function and Dysfunction

“…Moreover, GSK-3β co-localizes with NFTs [82]. Additionally, studies performed on cultured neurons have shown that the GSK-3 inhibitor, lithium, protects cells against neurodegeneration [83,84]. Abnormally phosphorylated tau protein is also the main component of neurofibrillary tangles found in Parkinson’s disease (PD) [85].…”

Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice

“…In this paradigm, water-deprived C57BL/6N mice were allowed to orientate themselves by distant visual cues when selecting the arm of the maze with a filled bottle. As a model of spatial learning, the Y-maze paradigm is considered to be a test for hippocampus-dependent memory (Gerlai, 2001;Liu et al, 2001;Finger et al, 2010;Alhassan et al, 2009;Tan et al, 2010). We also tested whether dimebon affects memory in a single trial inhibitory learning paradigm using the stepdown avoidance paradigm, another model for hippocampus-dependent memory (Lorenzini et al, 1996;Izquierdo and Medina, 1997;Strekalova et al, 2001Strekalova et al, , 2001) in young and middle-aged mice.…”