Alzheimer's disease (AD) currently impacts an estimated 5.5 million Americans and is the sixth leading cause of death in the United States. By 2050, the
number of Americans living with AD is predicted to rise to approximately 13.8 million. Women over 65 are the most susceptible to AD for reasons
unknown. Due to the lack of successful therapies for AD, the United States could be bordering on an AD epidemic. Several promising studies have
shown the compound 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA), a PKC-ε activator, to reverse the effects of AD in male
in vivo models. These studies are limited in their focus on male transgenic in vivo models, so this study explored a pharmacological AD model as well
as its impact on females. The Ferrous- Amyloid- Buthionine (FAB) model was used to induce AD pathologies. This model is established
by pumping ferrous sulfate, amyloid beta fragments, and buthionine sulfoximine into the lateral ventricle of rats over a four-week period. The FAB model
mirrors both behavioral and molecular pathologies of AD and models the role of oxidative stress in AD. Some rats also received ovariectomies (OVX) to model
post-menopause conditions, since the female population over 65 is the most susceptible to AD. Morris Water Maze (MWM) was used to evaluate spatial
learning and memory. This is a commonly used test of spatial learning and memory. Intraperitoneal injections of DCP-LA were administered 24 hours
prior to the first day of testing. Immunohistochemistry for NeuN and synaptophysin is currently being conducted to determine neuronal
and synaptic density differences between treatment groups. FAB treated animals showed a significant decrease in learning and memory as compared
to the controls. OVX rats only showed memory deficits as compared to the controls. The learning and memory performance by FAB animals that received
DCP-LA injections, returned to the level of the control. However, the injection of DCP-LA did not restore OVX animals' memory performances. The two
main conclusions that can be drawn from these results are that DCP-LA appears to reverse the negative effects of the FAB model, and OVX might be creating
memory deficits through pathways unrelated to PKC-ε. This study shows that the loss of sex hormones in females could majorly impact female neurological
health. These results also have exciting prospect for DCP-LA. This compound has now shown to reverse the negative effects of the FAB model in both male and
female rats. To date it has shown a lot of promise, but there are many follow up studies to conduct before it can reach human trials.
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