Effects And Mechanism Of Vitamin A Deficiency Increases The Risk Of Alzheimers’ Disease

OBJECTIVE:To study the nutrition status of vitamin A (VA) in aged people and the relationship between nutrition status of VA and AD and other cognitive handicap in aged people.SUBJECTS AND METHODS:After cognition function screening,106aged volunteers from a geracomium in the subuerbs of Chongqing were included in the study. After questionnaire and medical check-up, blood were drawn. Hb was measured with hemiglobincyanide measurement, and serum VA was measured with HPLC. Subjects were divided into Control group (cognitive normal group), AD group (Alzheimers’disease or suspect of Alzheimers’disease group) and CH group (cognitive handicap without AD group) according to their cognition function screening.RESULTS:(1) According to their cognition function,106aged volunteers were divided into Control group (n=47), AD group (n=46) and CH group (n=13).(2) The prevalence rate of VA normal was45.6%, Subclinical VAD was31.7%and VAD was22.7%in the106subjects. Serum VA concentration of Control group was the highest in the three groups, and AD group was the lowest. Mean values of serum VA in Control group, CH group, and AD group were1.32±0.11μmol/L,1.19±0.11μmol/L, and0.99±0.09μmol/L, respectively. There was significant difference in serum VA between Control group with AD group using Wilcoxon Two-Sample Test (P<0.03). There were no differences in serum VA between CH group and Control group, and CH group with AD group (P>0.05).CONCLUSIONS:(1) VA deficiency increases the risk of AD possibly.(2) The effects of VA nutrition status on the risk of AD with disease may more significant than on the risk of other cognitive handicap with disease. OBJECTIVE:To study the differences of RARs and IDE mRNA expression in Control group and AD group. And study the relationship between RARs and IDE mRNA expression and serum VA.SUBJECTS AND METHODS:After cognition function screening,106aged volunteers from a geracomium in the subuerbs of Chongqing were included in the study. After questionnaire and medical check-up, blood were drawn. Hb was measured with hemiglobincyanide measurement, and serum VA was measured with HPLC. Subjects were divided into Control group (cognitive normal group), AD group (Alzheimers’disease or suspect of Alzheimers’disease group) and CH group (cognitive handicap without AD group) according to their cognition function screening. The expression of RARs and IDE mRNA were measured with QPCR.RESULTS:(1) The expression of RARa mRNA of AD group was significant lower than Control group using Wilcoxon Two-Sample Test (P<0.05).(2) The expression of RARβ mRNA of AD group was higher than Control group (P>0.05).(3) The expression of RARy mRNA of AD group was lower than Control group (P>0.05).(4) The expression of IDE mRNA of AD group was lower than Control group(P>0.05).(5)Serum VA was correlated with the expression of RARa mRNA using Pearson Correlation Coefficients Test (P=0.052); Serum VA was not correlated with the expression of RARβ, RARγ and IDE mRNA (P>0.5)CONCLUSIONS:(1) VA seems to be necessary to RARα mRNA expression. And decreased expression of RARα, RARγ,IDE mRNA may incease(s) the risk of AD. For RARβ mRNA expression, an elevated expression may related to increased risk of AD. OBJECTIVE:To study the effects of MVAD during embryonic period on cognition handicap induced by Aβ1-42injection in gerontic rats and the relationship between serum VA, hippocampus VA and the cognition handicap induced by Aβ1-42injection.SUBJECTS AND METHODS:Twelve mother rats were divided randomly into Control group, marginal vitamin A deficiency (MVAD) group in this study. Male pups were included in the study. The dams and pups in Control group were fed with normal diet (VA6500IU/kg). The dams and pups in MVAD group were fed with MVAD diet (VA400IU/kg). Serum VA of pups from each rat cage were measured randomly at postnatal24hours,4weeks,8weeks,12weeks,18weeks,22weeks and26weeks respectively. At postnatal18weeks, the base line of MWM was tested. After that, Aβ1-42or PBS was injected into C3district of pups’ hippocampus with brain stereotaxis operation. All pups were divided into6groups randomly. Control Ⅰ group and MVAD Ⅰ group were injected in5×10-4μmol/5μl Aβ1-42each hippocampus. Control Ⅱ group and MVAD Ⅱ group were injected in2.5×10-4μmol/5μl Apβ-42each hippocampus. Control Ⅲ group and MVAD Ⅲ group were injected in5μl0.01M PBS each hippocampus.30days (postnatal23weeks) and80days (postnatal29weeks) after operation, the lengthways of MWM were performed. All pups were killed at postnatal30weeks. Serum VA and hippocampis VA were measured with HPLC.RESULTS:(1) At postnatal30weeks, serum VA of MVAD groups (0.94±0.05μmol/L) was significant lower than Control group (1.20±0.053μmol/L) using Wilcoxon Two-Sample Test (P<0.05). But hippocampus tissue VA of MVAD groups (0.048±0.004μmol/L) was significant higher than Control group (0.037±0.002μmol/L)(P<0.05). And Serum VA was not correlated with hippocampis VA.(2) The escape latency and path length in MVAD group was longer than in Control group at baseline (P<0.05). And the passing time of MVAD group was less than Control group at baseline.(3) The escape latency, path length and passing times of MVAD Ⅱ group were as the same of Control Ⅰ group at baseline using the GLM Procedure (P>0.05).30days after operation, the MWM records of MVAD Ⅱ group decreased.80days after operation, the escape latency, path length and passing times of MVAD Ⅱ group were longer than Control Ⅰ group. The escape latency, path length and passing times of Control Ⅱ group were little longer than Control Ⅲ group, and MVAD Ⅱ group was little longer than MVAD Ⅲ group using the Least Squares Means Test (with Tukey-Kramer adjustment, P>0.05).CONCLUSIONS:The influence of MVAD on hippocampus VA in rats may be compensated by itself because of RARs underdevelopment and low serum VA. The damage of hippocampus in MVAD group by Aβ1-42injection was severer than that of Control group. The resistance of MVAD group to Aβ1-42is less than that of Control group. And MVAD during embryonic period may increase the risk of AD. OBJECTIVE:To study the differences of RARs, IDE and ADAM10mRNA and protein expression in normal and embryonic MVAD rats and mechanism of Aβ1-42injection on the gene and protein expression of RARs, IDE and ADAM10.SUBJECTS AND METHODS:The method of animal model was same with part Ⅰ. The expression of RARs, AD AM10and IDE mRNA were measured with QPCR. The expression of RARs, ADAM10and IDE protein were measured with Western Blot.RESULTS:(1) The expression of RARa and RARy mRNA in Control Ⅰ group was the highest among all groups, and was significant highter than Control Ⅱ group and MVAD Ⅱ group using Least Squares Means test (P<0.05, with Tukey-Kramer adjustment). The expression of RARa and RARy mRNA in all groups was related to the amount of Aβ1-42injection.(2) The expression of RARa total protein in Control Ⅰ group was the highest among all groups, and was significant higher than Control Ⅱ group and MVAD Ⅱ group using Least Squares Means test.(3) The expression of RARa and RARy mRNA and the expression of RARa total protein in all groups was correlated with the amount of Aβ1-42injection.(4) The expression of RARβ mRNA and total protein in Control Ⅱ group was the highest among all groups, and was significant higher than Control Ⅰ group and MVAD Ⅱ group (P<0.05). The expression of RARβ mRNA and total protein in Control Ⅰ group and MVAD Ⅰ group was the lowest.(3) The expression of ADAM10mRNA, RARa mRNA and RARy mRNA was positively correlated with each other using Pearson correlation coefficients (r>0.994, P<0.0001). And the expression of ADAM10protein, RARa total protein and RARy total protein had the same tendency.(4) The expression of IDE mRNA and RARβ mRNA was positively correlated with each other (P<0.05). And the expression of IDE protein and RARβ protein had the same tendency.(5) The expression of RARa and RARβ nuclear protein in MVAD Ⅲ group was lower than that in Control Ⅲ group. The expression of RARa and RARβ nuclear protein in MVAD I group and MVAD Ⅱ group was higher than in Control Ⅰ group and Control Ⅱ group.(6) Serum VA was not significant correlated with hippocampus VA.(7) And serum VA and hippocampus VA were not correlated with the expression of RARs、AD AM10and IDE mRNA in hippocampus.CONCLUSIONS:(1) With Aβ1-42injection, RARa and RARy may promote the expression of ADAM10.(2) RARβ was not correlated with ADAM10. But RARβ may promote the expression of IDE. And then promote the degradation of Aβ1-42.(2) RARa, RARy and RARP may all participate in Aβ1-42degradation.(3) MVAD from embryonic period inhibits the development of RARs, and the expression of RARs down regulation in aged period. The underdevelopment of RARs increases the risk of AD.