BackgroundSystemic bacterial infections often result in enduring cognitive impairment and are a risk factor for dementia. There are currently no effective treatments for infection-induced cognitive impairment. Previous studies have shown that intermittent fasting (IF) can increase the resistance of neurons to injury and disease by stimulating adaptive cellular stress responses. However, the impact of IF on the cognitive sequelae of systemic and brain inflammation is unknown.MethodsRats on IF for 30 days received 1 mg/kg of lipopolysaccharide (LPS) or saline intravenously. Half of the rats were subjected to behavioral tests and the other half were euthanized two hours after LPS administration and the hippocampus was dissected and frozen for analyses.ResultsHere, we report that IF ameliorates cognitive deficits in a rat model of sepsis by a mechanism involving NF-κB activation, suppression of the expression of pro-inflammatory cytokines, and enhancement of neurotrophic support. Treatment of rats with LPS resulted in deficits in cognitive performance in the Barnes maze and inhibitory avoidance tests, without changing locomotor activity, that were ameliorated in rats that had been maintained on the IF diet. IF also resulted in reduced levels of mRNAs encoding the LPS receptor TLR4 and inducible nitric oxide synthase (iNOS) in the hippocampus. Moreover, IF prevented LPS-induced elevation of IL-1α, IL-1β and TNF-α levels, and prevented the LPS-induced reduction of BDNF levels in the hippocampus. IF also significantly attenuated LPS-induced elevations of serum IL-1β, IFN-γ, RANTES, TNF-α and IL-6 levels.ConclusionsTaken together, our results suggest that IF induces adaptive responses in the brain and periphery that can suppress inflammation and preserve cognitive function in an animal model of systemic bacterial infection.

The use of lithium is well established in bipolar disorders and the benefits are being demonstrated in neurodegenerative disorders. Recently, our group showed that treatment with microdose lithium stabilized the cognitive deficits observed in Alzheimer’s disease (AD) patients. In order to verify the lithium microdose potential in preventing the disease development, the aim of this work was to verify the effects of chronic treatment with microdose lithium given before and after the appearance of symptoms in a mouse model of a disease similar to AD. Transgenic mice (Cg-Tg(PDGFB-APPSwInd)20Lms/2J) and their non-transgenic litter mate genetic controls were treated with lithium carbonate (1.2 mg/Kg/day in drinking water) for 16 or 8 months starting at two and ten months of age, respectively. Similar groups were treated with water. At the end of treatments, both lithium treated transgenic groups and non-transgenic mice showed no memory disruption, different from what was observed in the water treated transgenic group. Transgenic mice treated with lithium since two months of age showed decreased number of senile plaques, no neuronal loss in cortex and hippocampus and increased BDNF density in cortex, when compared to non-treated transgenic mice. It is suitable to conclude that these data support the use of microdose lithium in the prevention and treatment of Alzheimer’s disease, once the neurohistopathological characteristics of the disease were modified and the memory of transgenic animals was maintained.

A lower incidence of dementia in bipolar patients treated with lithium has been described. This metal inhibits the phosphorylation of glycogen-synthase-kinase 3-α and β, which are related to amyloid precursor protein processing and tau hyperphosphorylation in pathological conditions, respectively. Following the same rationale, a group just found that lithium has disease-modifying properties in amnestic mild cognitive impairment with potential clinical implications for the prevention of Alzheimer's Disease (AD) when a dose ranging from 150 to 600 mg is used. As lithium is highly toxic in regular doses, our group evaluated the effect of a microdose of 300 μg, administered once daily on AD patients for 15 months. In the evaluation phase, the treated group showed no decreased performance in the mini-mental state examination test, in opposition to the lower scores observed for the control group during the treatment, with significant differences starting three months after the beginning of the treatment, and increasing progressively. This data suggests the efficacy of a microdose lithium treatment in preventing cognitive loss, reinforcing its therapeutic potential to treat AD using very low doses.

Alzheimer’s disease is a chronic and degenerative condition that had no treatment until recently. The current therapeutic strategies reduce progression of the disease but are expensive and commonly cause side effects that are uncomfortable for treated patients. Functional foods to prevent and/or treat many conditions, including neurodegenerative diseases, represent a promising field of study currently gaining attention. To this end, here we demonstrate the effects of pomegranate (Punica granatum) peel extract (PPE) regarding spatial memory, biomarkers of neuroplasticity, oxidative stress and inflammation in a mouse model of neurodegeneration. Male C57Bl/6 mice were chronically infused for 35 days with amyloid-β peptide 1–42 (Aβ) or vehicle (control) using mini-osmotic pumps. Another group, also infused with Aβ, was treated with PPE (p.o.– βA+PPE, 800 mg/kg/day). Spatial memory was evaluated in the Barnes maze. Animals treated with PPE and in the control group exhibited a reduction in failure to find the escape box, a finding that was not observed in the Aβ group. The consumption of PPE reduced amyloid plaque density, increased the expression of neurotrophin BDNF and reduced the activity of acetylcholinesterase enzyme. A reduction in lipid peroxidation and in the concentration of the pro-inflammatory cytokine TNF-α was also observed in the PPE group. No hepatic lesions were observed in animals treated with PPE. In conclusion, administration of pomegranate peel extract has neuroprotective effects involving multiple mechanisms to prevent establishment and progression of the neurodegenerative process induced by infusion with amyloid-β peptide in mice.

No abstract