ABSTRACT
<p><b>OBJECTIVE</b>To explore the mechanism of tau hyperphosphorylation and the effect of LiCl on tau phosphorylation and the memory retention deficits in streptozotocin-induced diabetes mellitus (DM) rats.</p><p><b>METHODS</b>The rats were randomly divided into control, DM, DM + NaCl, and DM + LiCl groups and diabetes was induced by streptozotocin. The activity of glycogen synthase kinase-3 (GSK-3) was measured by 32P-labelling. The level of tau phosphorylated and changes of memory retention were examined by Western blotting and step down test, respectively.</p><p><b>RESULTS</b>Compared with control group, the activity of GSK-3 and tau phosphorylation was increased, and the memory retention was impaired in DM group. When the rats were treated with LiCl, the activity of GSK-3 and hyperphosphorylation of tau were significantly arrested (P < 0.05, P < 0.01), and the memory retention deficit was significantly improved (P < 0.05).</p><p><b>CONCLUSION</b>The hyperphosphorylation of tau can be induced by activation of GSK-3 in diabetic rats. Lithium protects tau from hyperphosphorylation and may rescue memory retention in the rats by inhibiting GSK-3 activity.</p>
Subject(s)
Animals , Male , Rats , Cerebral Cortex , Metabolism , Diabetes Mellitus, Experimental , Glycogen Synthase Kinase 3 , Metabolism , Lithium Chloride , Therapeutic Uses , Memory Disorders , Drug Therapy , Metabolism , Phosphorylation , Rats, Sprague-Dawley , tau Proteins , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the alteration of beta-amyloid (Abeta) and glutamate transporter in the brain cortex of diabetes mellitus (DM) rats and the underlying mechanism.</p><p><b>METHODS</b>The rats were randomly divided into control, DM, DM +NaCl, and DM +LiCl groups and diabetes was induced by streptozotocin. The activity of glycogen synthase kinase-3 (GSK-3) and the function of glutamate transporter were measured by 32P-labelling. The amount of Abeta was determined by enzyme-linked immunosorbentassay.</p><p><b>RESULTS</b>In DM group, the level of Abeta40 increased (P < 0.01), but the function of glutamate transporter was impaired (P < 0.05). The activity of GSK-3 was stimulated (P < 0.05). Compared with DM group, the level of Abeta40 was restored (P < 0.01), and the function of glutamate transporter was enhanced (P < 0.05) in LiCl treated group, accompanied by a decreased activity of GSK-3.</p><p><b>CONCLUSION</b>Overproduction of Abeta and impaired glutamate transporter exist in DM rats, and increase of GSK-3 may play a crucial role in this process.</p>
Subject(s)
Animals , Male , Rats , Alzheimer Disease , Amino Acid Transport System X-AG , Metabolism , Amyloid beta-Peptides , Metabolism , Cerebral Cortex , Metabolism , Diabetes Mellitus, Experimental , Drug Therapy , Glycogen Synthase Kinase 3 , Metabolism , Lithium Chloride , Pharmacology , Random Allocation , Rats, Sprague-DawleyABSTRACT
Objective To explore the alterations of protein phosphatase-2A (PP-2A) in lymphocytes in mild cognition impairment (MCI) and Alzheimer's disease (AD).Methods The activity PP-2A of was measured by ~(32)p liquid seintillography for incorporated radioactivity in control group(n=11) , the MCI group(n=11),and the AD group(n=11).The expression of PP-2A was determined by Western blot.Results In the control group,the activity of PP-2A (1.01?0.09) and the expression of PP-2A (0.96?0.07) were high while in the MCI group,the activity of PP-2A (0.71?0.12) and the expression of PP-2A (0.80?0.05) were decreased (both P