Influence Of ApoE And Stress On Emotion, Learning And Memory In Mice

Apolipoprotein (ApoE) is a 34 KD protein that participates in the transport of plasma lipids and redistribution of lipoproteins and cholesterol. There are three isoforms of ApoE in human, (ε2,ε3, andε4). Of the three common human ApoE isoform, inheritance of ApoE4 is a great genetic risk factor for the development of sporadic Alzheimer’s disease (AD) and other diseases. In the present study, we investigated the role of ApoE in the following aspects:1 The role of ApoE in the anxiety-like behaviorAnxiety symptoms occur in a large part of AD patients. ApoE4, as a great risk factor of AD, also has been recognized as an important contributor for psychiatric disorders. In the present study, we aimed to investigate anxiety related behavior changes in different ApoE isoforms transgenic mice. Our results show that 3mons ApoE4 transgenic mice showed more anxiety-like behaviors than that in ApoE3 mice. To assess the function of Hypothalamic-pituitary-adrenal axis (HPA), we measured corticosterone secretion responsed to acute restraint stress. The level of corticosterone secretion increased rapidly reponsed to stress in both ApoE3 and ApoE4 transgenic mice. However, no significant difference was found between the ApoE3 and ApoE4 mice. We measured the estrogen level in the central never system. We found a lower estrogen level in ApoE4 transgenic mice than that in ApoE3 mice. Also, we found that several receptors were dysregulated in ApoE4 postnatal mice and 3mons adult mice compared with ApoE3 mice, rather than in aged mice. In summary, ApoE4 inbibited CRH expression by dowregulating biosynthesis of estrogen, which mediated by the ERE in the promoter of CRH.2 The behavior changes in ApoE mice response to chronic stressThere is evidence that both genetic and environmental factors may play a role in the pathogenesis of Alzheimer’s disease (AD). This study was designed to investigate the behavioral and synapse changes under chronic stress administration in different human ApoE transgenic mice. We found that the exploration and locomotor activity were lower in ApoE4 mice compared with that in ApoE3 mice. After chronic stress treatment, ApoE3 mice showed a lower level of exploration and locomotor activity, while ApoE4 mice became more active in exploration and travel. A higher level of anxiety-like behaviors was found in non-stressed ApoE4 mice than that in non-stressed ApoE3 mice. After chronic stress treatment, both ApoE3 and ApoE4 mice became anxious in the light dark box test. In the open field test, stressed ApoE3 mice showed a higher level of anxiety, while stressed ApoE4 mice, unexpectedly, became less anxious. In the novel object recognition task, we found that stressed ApoE4 mice showed impairment in novel object recognition in one-hour interval task and both stressed ApoE3 and ApoE4 mice showed cognitive deficits in twenty-four hour interval task. In the Y-maze, impairment in spontaneous alternation to the novel arm was found in non-stressed ApoE4 mice and stressed ApoE3 mice. However, we did not find any significant difference in the expression of synapsinI and PSD95 among the four groups. In summary, we found that chronic stress decreased the spontaneous locomotor activity and exploration behavior, increased anxiety-like behavior in ApoE3 mice; and increased locomotor activity and exploration behavior, decreased anxiety-like behavior in ApoE4 mice.3 Association of ApoE genotypes with the age at natural menopause in Chinese femalesObjective: The age at natural menarche and menopause are influenced by several genetic factors. This study aimed to investigate possible relationship between ApoE genotype and the age at menarche and natural menopause in Chinese females. Results: Elderly group: one-way ANOVA analysis revealed that ApoE genotype was significantly associated with the age at natural menopause (P = 0.010). Compared with ApoEε3/3 carriers, ApoEε3/4 female showed a delay about 1.8 year (P=0.002) at the age of natural menopause. Young group: ApoE single allele positive/negative analysis showed the age at menarche in ApoEε4 carriers was slightly earlier than ApoEε4 negative carriers’(P=0.048). Conclusions: We demonstrated that ApoE genotype is linked to the age at natural menopause significantly and the age at menarche slightly. The results indicate that ApoEε4 is associated with prolonged reproductive period in Chinese females.