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

PLoS One. 2015 Nov 25;10(11):e0142267. doi: 10.1371/journal.pone.0142267. eCollection 2015.


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 (0.25mg/Kg/day in drinking water) for 16 or 8 months starting at two and ten months of age, respectively [corrected]. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Amnesia / genetics
  • Amnesia / pathology
  • Amnesia / physiopathology
  • Amnesia / prevention & control*
  • Animals
  • Avoidance Learning / drug effects
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / pathology
  • Cerebral Cortex / physiopathology
  • Cognition Disorders / genetics
  • Cognition Disorders / pathology
  • Cognition Disorders / physiopathology
  • Cognition Disorders / prevention & control*
  • Disease Models, Animal
  • Drug Administration Schedule
  • Gene Expression
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Humans
  • Lithium Carbonate / pharmacology*
  • Locomotion / drug effects
  • Male
  • Maze Learning / drug effects
  • Memory / physiology
  • Mice
  • Mice, Transgenic
  • Neuroprotective Agents / pharmacology*
  • Plaque, Amyloid / genetics
  • Plaque, Amyloid / pathology
  • Plaque, Amyloid / physiopathology
  • Plaque, Amyloid / prevention & control*


  • Brain-Derived Neurotrophic Factor
  • Neuroprotective Agents
  • Lithium Carbonate

Grant support

This work was supported by grants from FAP-Santa Casa/2011, Fundação de Amparo a Pesquisa no Estado de Sao Paulo (FAPESP 2012/12917-3). Nunes, M.A, Baraldi-Tornisielo, T., were fellowship recipients from CAPES-PROSUP; Monteiro-Silva, K. and Sousa, S.I.G. were fellowship recipients from PIBIC/CNPq; Balthazar, J. and Albuquerque, M.S. were fellowship recipients from CAPES; and Schöwe, N.M. was fellowship recipient from FAPESP (2013/19999-8). Buck, H.S. is a fellowship recipient from CNPq (303283/2014-9). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.