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.
Highlights
Demographic changes resulting from the increase in life span and the increasing number of aged people lead to a dramatic increase in the prevalency of dementias
Male hemizygous transgenic mice—here called TG—B6.Cg-Tg (PDGFB-APPSwInd)—that express a mutant form of the human amyloid precursor protein carrying the Swedish (K670N, M671L) and Indiana (V717F) familial Alzheimer’s disease (AD) mutations directed by the platelet-derived growth factor (PDGF) β-chain promoter (APP mice, J20 line) and age-matched wild type litter mates—here called WT—were provided from our own colony, using breeding males acquired from “The Jackson Laboratories”, USA (Stock Number 006293) [11]
This work follows on previous results with the microdose of lithium (1.5 mg/day) as a stabilizer of cognitive loss in patients diagnosed with Alzheimer’s disease (AD) [5]
Summary
Demographic changes resulting from the increase in life span and the increasing number of aged people lead to a dramatic increase in the prevalency of dementias. Patients present progressive atrophy of gray matter, which can be a reflection of neuronal death caused by micro-structural changes in brain [2]. Gradual accumulation of neurofibrillary tangles, mainly intracellularly, formed as a result of abnormal hyperphosphorylation of cytoskeletal tau protein and deposition of amyloid-β peptide fibrils into senile plaques, mainly extracellularly, are the most important histopathological characteristics of AD that lead to huge neuronal death [3]. The biochemical mechanisms that are activated to produce these alterations are many and are present in specific vulnerable brain areas. One of the brain areas most succeptible is the hippocampus [4]
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