Aging / Alzheimer's Disease
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/31250
Browse
Browsing Aging / Alzheimer's Disease by Subject "Aging"
Now showing 1 - 2 of 2
- Results Per Page
- Sort Options
Item EFFECTS OF SHORT-TERM PHYTOESTROGEN SUPPLEMENTATION ON THE BEHAVIOR OF MALE AND FEMALE MICE(2013-04-12) Sidhu, AkramPurpose: Plant-derived, non-steroidal compounds called phytoestrogens have been widely used as substitutes for estrogen in anticipation of estrogen-like therapeutic effects without producing the side effects associated with estrogen therapy. Human and animal data are still controversial regarding the beneficial effects of such compounds and whether they are differential based on the gender/sex of the subjects. This study investigated the effects of short-term phytoestrogen intake on the age-associated behavioral changes in the young, middle and old mice of both sex. Methods: Separate groups of young (6 months), middle (12 months) and old (24 months) male and female C57BL/6J mice were placed on either a phytoestrogen-free (PF) diet (N=15-17) or a phytoestrogen-rich (PR) diet containing (350-650 mg/kg phytoestrogens (N=16-19) for a period of 16 weeks. After 5 weeks on the diets, the mice were subjected to a series of behavioral tests to measure spontaneous activity (locomotor activity), anxiety (elevated plus maze, EPM), and cognitive function (water maze and active avoidance test). Results: PR mice exhibited increased spontaneous activity when compared to the PF mice, regardless of sex and especially in their rearing activity. In the EPM task, female mice spent less time in the open arms when compared to their males counterpart. At 24 months, PR male mice spent less time in open arms than their age-matched controls. In the water maze, PR mice performed worse than the PF mice which was particularly noticeable in the old mice, however there was no effect of the diet in the males. No major effects of diets were found in the active avoidance paradigm. Conclusions: Overall, short-term supplementation with phytoestrogens did not seem to affect anxiety levels or cognitive, though it may adversely impact spatial learning and memory in female mice, especially of old age.Item REELIN SIGNAL TRANSDUCTION PATHWAY IN APOE3 AND APOE4 TRANSGENIC MICE(2013-04-12) Dugal, MariceliePurpose: The ɛ4 allele of apolipoprotein E (APOE) has been associated with increased risk for the development of late-onset, familial and sporadic Alzheimer's disease (AD). The mechanisms underlying the increase risk of AD development conferred by the ɛ4 allele remains unclear. Reelin and its associated signal transduction pathway are involved in developmental processes, and more specifically, in regulating neuronal migration and cortical lamination in the embryotic brain. Recently, it has been determined that reelin is present in the adult brain throughout the neocortex and hippocampus suggesting a potential role in synaptic plasticity. Furthermore, studies have shown that disruption of the reelin pathway led to decreased memory, impaired long-term potentiation (LTP), and affected dendritic spine morphology. This preliminary study investigated the role of the reelin pathway as a potential mechanism underlying the functional declines associated with APOE polymorphism. Methods: Separate groups of young (7 months) male and female mice expressing human apolipoprotein E4 or E3 in glial cells) were subjected to a series of behavioral tests to measure spontaneous activity, reflexes (walking initiation, alley turn, and negative geotaxis), motor function (wire suspension, bridge walking, coordinated running), and cognitive function (spatial water maze, active avoidance). Brain regions were dissected to determine the levels of reelin and other contributors of its pathway such as dab1, fyn, AMPA and NR2A via western blot analyses. Results: ApoE3 mice took longer latencies to fall in bridge walking, wire suspension, and coordinated running tasks than their ApoE4 counterparts, most notably in males. In the active avoidance task, ApoE3 female mice took fewer trials to reach criterion in session 3 over their ApoE4 counterparts. Western blot analyses will reveal whether reelin may underlie the differences in brain function between genotype and sex. Conclusions: Our results indicate that there may be functional differences between sex as well as ApoE polymorphism. Western blot analyses will reveal whether reelin, dab1, fyn, AMPA and NR2A may underlie the differences in brain function between genotype and sex.