Neuroprotective Effects of a Combined Therapy With Memantine, Donepezil and Vitamin D in Ovariectomized Female Mice Subjected to Dementia Model

The postmenopausal period is characterized by a decrease in the hormonal supply which is associated with Alzheimer's Disease (AD). Vitamin D is neuroprotective and can be used in combination with pre-existing medications to improve its effects. The objective was to evaluate the effect of vitamin D associated with memantine and donepezil in female mice submitted to ovariectomy (OVX) for 5 months and subjected to an AD-induced dementia model. Animals were divided into 5 groups who received 17 days of treatment and were subjected to behavioral tests. The animals underwent euthanasia at 18 th day. OVX groups exhibit reduced levels of E2 and triple treatment group had high levels of vitamin D. The induction of dementia with OVX induced short- and long-term spatial and habituation memories damage. Also, induced reduction of BDNF and IL-4 levels in hippocampus, and increasing levels of TNFα in hippocampus and of IL-1β in hippocampus and frontal cortex of animals, as well as a significant increase on GFAP immunoreactivity. Triple-association treatment reversed the effects of long-term spatial and habituation memories damage, as well as reversed changes in TNFα, IL-1β, IL-4 and GFAP immunoreactivity levels in hippocampus of treated animals. Therapeutic association has beneficial effects on memory and inflammation parameters in female mice subjected to OVX and the AD animal model of dementia.