1.Inhibition of tau hyperphosphorylation and beta amyloid production in rat brain by oral administration of atorvastatin.
Fen LU ; Xu LI ; Ai-Qin SUO ; Jie-Wen ZHANG
Chinese Medical Journal 2010;123(14):1864-1870
BACKGROUNDAlzheimer's disease (AD) is a neurodegenerative disorder and the leading cause of dementia in the elderly. The two hallmark lesions in AD brain are deposition of amyloid plaques and neurofibrillary tangles (NFTs). Hypercholesteremia is one of the risk factors of AD. But its role in the pathogenesis of AD is largely unknown. The aim of this study was to investigate the relationship between hypercholesteremia and tau phosphorylation or beta-amyloid (Abeta), and evaluate the effect of atorvastatin on the level of tau phosphorylation and Abeta in the brains of rats fed with high cholesterol diet.
METHODSSprague-Dawley (SD) rats were randomly divided into normal diet control group, high cholesterol diet group, and high cholesterol diet plus atorvastatin (Lipitor, 15 mg x kg(-1) x d(-1)) treated group. Blood from caudal vein was collected to measure total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high-density lipoprotein (HDL) at the end of the 3rd and the 6th months by an enzymatic method. The animals were sacrificed 6 months later and brains were removed. All left brain hemispheres were fixed for immunohistochemistry. Hippocampus and cerebral cortex were separated from right hemispheres and homogenized separately. Tau phosphorylation and Abeta in the brain tissue were determined by Western blotting (using antibodies PHF-1 and Tau-1) and anti-Abeta40/anti-Abeta42, respectively.
RESULTSWe found that high cholesterol diet led to hypercholesteremia of rats as well as hyperphosphorylation of tau and increased Abeta level in the brains. Treatment of the high cholesterol diet fed rats with atorvastatin prevented the changes of both tau phosphorylation and Abeta level induced by high cholesterol diet.
CONCLUSIONSHypercholesteremia could induce tau hyperphosphorylation and Abeta production in rat brain. Atorvastatin could inhibit tau hyperphosphorylation and decrease Abeta generation. It may play a protective role in the patho-process of hypercholesteremia-induced neurodegeneration in the brain.
Administration, Oral ; Amyloid beta-Peptides ; metabolism ; Animals ; Antibodies, Monoclonal ; Atorvastatin Calcium ; Blotting, Western ; Brain ; drug effects ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Heptanoic Acids ; administration & dosage ; pharmacology ; therapeutic use ; Immunohistochemistry ; Male ; Phosphorylation ; drug effects ; Pyrroles ; administration & dosage ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; tau Proteins ; metabolism
2.Effect of folate and vitamin B_(12) on tau phosphorylation in hippocampus of elderly rats
Jie-Wen ZHANG ; Fen LU ; Xu LI ; Ai-Qin SUO ; Wei LI ; Liang-Fu ZHU ; Li XIANG ; Yue HUANG
Chinese Journal of Neurology 2001;0(01):-
Objective To investigate the relationship of folates,vitamin B_(12) with tan phosphorylation and the possible mechanism in Alzhcimer's disease (AD).Method Tau protein phosphorylation was examined in hippocampns of rats of two months old and forty months old treated or untreated by folates and vitamin B_(12) using Western blot and immunohistochemistry with phosphorylation dependent and independent tau antibodies.Results We found that tau phosphorylation in aged rat brain showed a significant higher level than that in the two-month olds.Folates combined with vitamin.B_(12) could decrease tau phosphorylation by 27% at the site of Ser396/404 of hippoeampus in aged rats.Conclusion It suggests folates and vitamin B_(12) may play an important role in preventing the neurodegenerative change via effeeting tau phosphorylation in AD brain.
3.Effects of estrogen on P-Tau, ChAT and nerve growth factor protein expressions in the brain tissue of rats with Alzheimer's disease.
Yue HUAGN ; Yu-ming XU ; Jie-wen ZHANG ; Xiu-hua REN ; Ai-qin SUO
Journal of Southern Medical University 2010;30(10):2408-2410
OBJECTIVETo examine the effect of estrogen on the expressions of phosphorylated Tau (P-Tau), ChAT and nerve growth factor (NGF) protein in the brain tissue of rat models of Alzheimer disease (AD).
METHODSRat models of AD were established by injecting Aβ1-42 protein fragments in the right lateral ventricle. Two weeks later, 17β-estradiol tablets were implanted subcutaneously at the neck of the rats and maintained for 30 days. The pathological changes in the rats' brain neurons and alterations in the expressions of P-Tau, ChAT and NGF proteins were observed using HE staining and immunohistochemistry, respectively.
RESULTSIn the AD rats, neurofibrillary tangles occurred in the brain tissue, and estrogen treatment significantly reduced the formation of neurofibrillary tangles. Estrogen treatment also resulted in lowered P-Tau expression and increased ChAT and NGF protein expressions in comparison with those in the AD model rats.
CONCLUSIONEstrogen can up-regulate ChAT and NGF and down-regulate tau protein expression, thus producing obvious therapeutic effect on AD in rats.
Alzheimer Disease ; metabolism ; pathology ; Animals ; Brain ; drug effects ; metabolism ; Disease Models, Animal ; Estradiol ; pharmacology ; Male ; Nerve Growth Factors ; metabolism ; Neurons ; metabolism ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; tau Proteins ; metabolism
5.Acceptability and influencing factors on pre-exposure prophylaxis programs among female sex workers in Guangxi, China
Suo-Su WEI ; Yun-Feng ZOU ; Teng-Yan WU ; Jun-Jun JIANG ; Xin-Qin LIN ; Ming-Qiang LI ; De-Ren WU ; Na XU ; Fu-Mei WEI ; Pei-Yan XIE ; Xiao-Ni ZHONG ; Hao LIANG ; Ai-Long. HUANG
Chinese Journal of Epidemiology 2011;32(11):1091-1094
Objective To study the acceptability of pre-exposure prophylaxis (PrEP)program on prevention of human immunodeficiency virus (HIV)infection among female sex workers (FSWs) in Guangxi of China.Methods A cross-sectional survey using convenience sampling was administered among 405 FSWs in Nanning,Liuzhou and Beihai cities of Guangxi,China.Self-designed questionnaire,face to face interviews were used to collect HIV-related risk behaviors,knowledge and acceptability of PrEP.Results After an introduction on PrEP,presuming that it was effective,safe and free of charge,85.9% of the 405 FSWs said they would use it.Data from logistic regression analysis showed that significant factors of intent to use PrEP would include the followings:workplace (OR=2.256,P=0.009),monthly income (OR=0.257,P=0.004),family closeness (OR=0.338,P=0.012),knowledge on HIV/AIDS (OR=2.802,P=0.028),HIV/AIDS risk was introduced from a strange client (OR=0.363,P=0.049),whether the gatekeeper ordering the use of condom (OR=0.432,P=0.010),whether consistent using condom with clients (OR=3.010,P=0.002),whether ever using drugs to prevent STD infection (OR=3.570,P=0.049) etc.Conclusion Awareness on HIV/AIDS knowledge and self-protection seemed the main influential factors while health education might promote the acceptability of PrEP.