title: 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 (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.
authors.affiliation: Department of Physiological Sciences, Santa Casa de São Paulo School of Medical Sciences, R. Dr. Cesario Motta Junior, 61, 11° andar, São Paulo, SP 01221-020, Brazil.|Research Group on Neuropharmacology of Aging-ReGNA, Sao Paulo, Brazil.
authors.forename: Marielza Andrade
authors.initials: MA
authors.lastname: Nunes
authors.affiliation: Graduation Course on Pharmacology, Institute of Biomedical Sciences, Universidade de São Paulo, Avenida Professor Lineu Prestes, 1524, 05508-900 São Paulo, Brazil.|Research Group on Neuropharmacology of Aging-ReGNA, Sao Paulo, Brazil.
authors.forename: Natalia Mendes
authors.initials: NM
authors.lastname: Schöwe
authors.affiliation: Department of Physiological Sciences, Santa Casa de São Paulo School of Medical Sciences, R. Dr. Cesario Motta Junior, 61, 11° andar, São Paulo, SP 01221-020, Brazil.
authors.forename: Karla Cristina
authors.initials: KC
authors.lastname: Monteiro-Silva
authors.affiliation: Department of Physiological Sciences, Santa Casa de São Paulo School of Medical Sciences, R. Dr. Cesario Motta Junior, 61, 11° andar, São Paulo, SP 01221-020, Brazil.|Research Group on Neuropharmacology of Aging-ReGNA, Sao Paulo, Brazil.
authors.forename: Ticiana
authors.initials: T
authors.lastname: Baraldi-Tornisielo
authors.affiliation: Department of Physiological Sciences, Santa Casa de São Paulo School of Medical Sciences, R. Dr. Cesario Motta Junior, 61, 11° andar, São Paulo, SP 01221-020, Brazil.
authors.forename: Suzzanna Ingryd Gonçalves
authors.initials: SI
authors.lastname: Souza
authors.affiliation: Graduation Course on Pharmacology, Institute of Biomedical Sciences, Universidade de São Paulo, Avenida Professor Lineu Prestes, 1524, 05508-900 São Paulo, Brazil.
authors.forename: Janaina
authors.initials: J
authors.lastname: Balthazar
authors.affiliation: Department of Physiological Sciences, Santa Casa de São Paulo School of Medical Sciences, R. Dr. Cesario Motta Junior, 61, 11° andar, São Paulo, SP 01221-020, Brazil.|Research Group on Neuropharmacology of Aging-ReGNA, Sao Paulo, Brazil.
authors.forename: Marilia Silva
authors.initials: MS
authors.lastname: Albuquerque
authors.affiliation: Department of Physiological Sciences, Santa Casa de São Paulo School of Medical Sciences, R. Dr. Cesario Motta Junior, 61, 11° andar, São Paulo, SP 01221-020, Brazil.|Research Group on Neuropharmacology of Aging-ReGNA, Sao Paulo, Brazil.
authors.forename: Ariadiny Lima
authors.initials: AL
authors.lastname: Caetano
authors.affiliation: Graduation Course on Pharmacology, Institute of Biomedical Sciences, Universidade de São Paulo, Avenida Professor Lineu Prestes, 1524, 05508-900 São Paulo, Brazil.|School of Arts, Sciences and Humanities, Universidade de São Paulo, Av. Arlindo Bettio, 1000, São Paulo, SP 03828-080, Brazil.|Research Group on Neuropharmacology of Aging-ReGNA, Sao Paulo, Brazil.
authors.forename: Tania Araujo
authors.initials: TA
authors.lastname: Viel
authors.affiliation: Department of Physiological Sciences, Santa Casa de São Paulo School of Medical Sciences, R. Dr. Cesario Motta Junior, 61, 11° andar, São Paulo, SP 01221-020, Brazil.|Research Group on Neuropharmacology of Aging-ReGNA, Sao Paulo, Brazil.
authors.forename: Hudson Sousa
authors.initials: HS
authors.lastname: Buck
mesh_terms: D000284:Administration, Oral; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D000647:Amnesia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003072:Cognition Disorders / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D015870:Gene Expression; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D016651:Lithium Carbonate / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000494:pharmacology*; D058225:Plaque, Amyloid / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D016651:Lithium Carbonate