Chronic Microdose Lithium Treatment Prevented Memory Loss and Neurohistopathological Changes in a Transgenic Mouse Model of Alzheimer's Disease

Abstract

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.

Neuroprotective Effects of Pomegranate Peel Extract after Chronic Infusion with Amyloid-β Peptide in Mice

“…Spontaneous locomotor activity was measured as described previously [18, 21] using an animal activity cage (model 7430, Ugo Basile, Comerio, Italy). The apparatus consisted of a transparent acrylic cage (35 cm x 23 cm x 20 cm) with a set of horizontal sensors to register locomotor activity and a set of vertical sensors to register rearing.…”

“…Spatial memory was evaluated using the Barnes maze and a protocol based on previous studies [21, 22]. Briefly, the equipment consisted of a white arena (diameter 100 cm) positioned 1 m from the floor.…”

“…Frozen brain samples were warmed to room temperature (22°C) and were air-dried for 5–10 min. Quantification of senile plaques was performed as described previously [21]. Slides were washed 5 times in PBS and incubated in 0.1% Thioflavine S solution in PBS, containing 0.1% Triton, for 5 min.…”

Dementia, Preclinical Studies in Neurodegeneration and its Potential for Translational Medicine in South America

“…Further Chile is working on methods to better understanding of neurodegeneration and looking for new treatment strategies and biomarkers for early detection of AD (Rojo et al, 2010; Beauquis et al, 2014; Vargas et al, 2014; Martino Adami et al, 2015; Nunes et al, 2015) and VaD (Valério Romanini et al, 2013; Schiavon et al, 2014; Silva et al, 2015; Primo et al, 2016). In Colombia, some experimental designs have been developed on ischemic stroke and Alzheimer’s animal models trying to propose therapeutical approach that would be versatile in the time (prevention, blocking progress and reversion) as mentioned later.…”

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“…Já os animais que não possuíam a transgenia não tiveram diferença em seu desempenho cognitivo nem nos parâmetros analisados, independentemente do tratamento com lítio ou água (NUNES et al, 2015).…”