Vitamin D3 improves spatial memory and modulates cytokine levels in aged rats.

Vitamin D3 deficiency is associated with an increased risk of dementia. An association between vitamin D3 deficiency and subjective cognitive complaints in geriatric patients has been previously reported. This study aimed to evaluate the effects of two doses of vitamin D3 on spatial memory (using the Radial Maze) and cytokine levels [tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and interleukin-10 (IL-10)] on 2-, 6-, 13-, 22-, and 31-month-old male Wistar rats. Animals were supplemented with vitamin D3 at doses of 42 IU/kg and 420 IU/kg for 21 days. A radial maze test was performed to evaluate spatial memory. After the behavioral test, the frontal cortex and hippocampus were dissected for enzyme immunoassay analyses to measure the cytokine levels (TNFα, IL-1ß, IL-6, and IL-10). Our results showed that vitamin D3 supplementation reversed spatial memory impairment at the supplemented doses (42 and 420 IU/kg) in 6-, 13-, and 22-month-old animals and at a dose of 420 IU/kg in 31-month-old animals. The lower dose (42 IU/kg) regulates both pro- and anti-inflammatory cytokines mainly in the frontal cortex. Our results suggest that vitamin D3 has a modulatory action on pro- and anti-inflammatory cytokines, since older animals showed increased cytokine levels compared to 2-month-old animals, and that vitamin D3 may exert an immunomodulatory effect on aging.

Neuroprotective effects of combined therapy with memantine, donepezil, and vitamin D in ovariectomized female mice subjected to dementia model.

Women older than 60 have a higher risk of dementia, aging-related cognitive decline, and Alzheimer's Disease (AD) than the rest of the population. The main reason is hormonal senescence after menopause, a period characterized by a decline in estrogen levels. Since the effectiveness of drugs currently approved for the treatment of AD is limited, it is necessary to seek the development of new therapeutic strategies. Vitamin D deficiency is prevalent in AD patients and individuals with dementia in general. The supplementation of this vitamin in dementia patients might be an interesting approach for increasing the effectiveness of pre-existing medications for dementia treatment. Thus, the present study aims to investigate the effect of vitamin D treatment associated with memantine and donepezil in female mice submitted to ovariectomy (OVX) for five months and subjected to a dementia animal model induced by intracerebroventricular injection of aggregated amyloid ßeta (Aß1-42). For this purpose, Balb/c mice were divided into five experimental groups, which received 17 days of combined therapy with vitamin D, donepezil, and memantine. Then, animals were subjected to behavioral tests. OVX groups exhibited reduced levels of estradiol (E2) in serum, which was not altered by the combined therapy. Higher levels of vitamin D3 were found in the OVX animals submitted to the triple-association treatment. Mice exposed to both OVX and the dementia animal model presented impairment in short and long-term spatial and habituation memories. Also, female mice exposed to Aß and OVX exhibited a reduction in brain-derived neurotrophic factor (BDNF) and interleukin-4 (IL-4) levels, and an increase in tumor necrose factor-α (TNFα) levels in the hippocampus. Besides, increased levels of IL-1ß in the hippocampus and cerebral cortex were observed, as well as a significant increase in immunoreactivity for glial fibrillary acidic protein (GFAP), an astrocytes marker, in the hippocampus. Notably, triple-association treatment reversed the effects of the exposition of mice to Aß and OVX in the long-term spatial and habituation memories impairment, as well as reversed changes in TNFα, IL-1ß, IL-4, and GFAP immunoreactivity levels in the hippocampus of treated animals. Our results indicate that the therapeutic association of vitamin D, memantine, and donepezil has beneficial effects on memory performance and attenuated the neuroinflammatory response in female mice subjected to OVX associated with a dementia animal model.

Long-term administration of soft drink causes memory impairment and oxidative damage in adult and middle-aged rats.

INTRODUCTION: The consumption of soft drinks has increased considerably in recent decades, mainly cola soft drinks. Excessive consumption of cola-based soft drinks is associated with several diseases and cognitive decline, particularly memory impairment. Furthermore, diets with high sugar can promote insulin resistance, metabolic syndrome, and dyslipidemia. AIM: Thus, the present study aimed to evaluate the effect of cola soft drink intake on behavioral alterations and oxidative damage in 2-, 8- and 14- month-old male Wistar rats. METHODS: The soft drink groups drank soft drink and/or water ad libitum during 67 days, the control groups ingested only water. Radial-arm maze and Y-maze were used to evaluate spatial memory, open-field to evaluate the habituation memory, and inhibitory avoidance to evaluate aversive memory. The behavioral tests started at the day 57 and finished at day 67 of treatment. At 68th day, the rats were killed; frontal cortex and hippocampus were dissected to the analysis of antioxidants enzymes catalase (CAT) and superoxide dismutase (SOD); and the oxidative markers thiobarbituric acid reactive substances (TBARS) and dichloro-dihydro-fluorescein diacetate (DCFH) were measured in the hippocampus. RESULTS AND DISCUSSION: The cola-based soft drink intake caused memory impairment in the radial-arm maze, Y-maze task, and open-field in the 2- and 8-month-old rat, but not in the 14-month-old. There were no difference among groups in the inhibitory avoidance test. In the frontal cortex, soft drink intake reduced CAT activity in the 8-month-old rats and SOD activity in the 8- and 14-month-old rats. In the hippocampus, the soft drink increased CAT activity in 2- and 8-month-old rats, increased DCFH levels at all ages, and increased TBARS levels in 2-month-rats. Therefore, the results show that long-term soft drink intake leads to memory impairment and oxidative stress. The younger seems to be more susceptible to the soft drink alterations on behavior; however, soft drink caused alterations in the oxidative system at all ages evaluated.