title: Stereological investigation of the CA1 pyramidal cell layer in untreated and lithium-treated 3xTg-AD and wild-type mice.
abstract: Pyramidal neuron loss in the hippocampal CA1 region is a very early hallmark of Alzheimer disease (AD). Lithium might be a therapeutic strategy for AD due to its neuroprotective and neurotrophic properties. This study used modern stereological techniques to investigate possible CA1 pyramidal neuron loss in 11-month-old triple transgenic AD (3xTg-AD) mice, and also the effects of therapeutic and subtherapeutic lithium doses on the number and density of CA1 pyramidal neurons and volume of CA1 pyramidal layer in 3xTg-AD and wild-type mice treated from 3 to 11 months of age. 3xTg-AD mice displayed CA1 pyramidal layer atrophy that is likely due to reduced neuronal volume because of the absence of neuronal loss. Both lithium treatments of 3xTg-AD mice, which already expressed AD-like pathology, had no effect on CA1 atrophy. However, lithium treatment of wild-type mice, at low (subtherapeutic) doses, induced a significant increase in total CA1 pyramidal neuron number that led to a significant increase in total CA1 pyramidal layer volume. The lithium-induced increase in CA1 neuron number is highly consistent with previous evidence that adult neurogenesis can be exogenously induced in the CA1 pyramidal layer with impact on total CA1 neuron number, thus raising the possibility of the chronic use of low-dose lithium as a strategy to help compensate for neuronal loss in CA1 and perhaps other typically non-neurogenic brain regions in various neurological diseases. With regard to AD, low-dose lithium intervention must be initiated as early as possible in the course of neuropathology for beneficial effects to occur.
authors: Laboratory of Neuroscience (LIM-27), Institute of Psychiatry of Clinical Hospital, Faculty of Medicine, University of Sao Paulo, Rua Dr. Ovídio Pires de Campos 785, 05403-010 Sao Paulo, SP, Brazil; Institute of Biomedicine, University of Aarhus, Wilhelm Meyers Allé 3, Building 1234, 8000 Aarhus C, Denmark. Electronic address: schaffer@usp.br.
authors: Evelin L
authors: EL
authors: Schaeffer
authors: Lipids Laboratory (LIM-10), Endocrinology and Metabolism Division of Clinical Hospital, Faculty of Medicine, University of Sao Paulo, Av. Dr. Arnaldo 455, 01246-000 Sao Paulo, SP, Brazil.
authors: Sergio
authors: S
authors: Catanozi
authors: Institute of Biomedicine, University of Aarhus, Wilhelm Meyers Allé 3, Building 1234, 8000 Aarhus C, Denmark.
authors: Mark J
authors: MJ
authors: West
authors: Laboratory of Neuroscience (LIM-27), Institute of Psychiatry of Clinical Hospital, Faculty of Medicine, University of Sao Paulo, Rua Dr. Ovídio Pires de Campos 785, 05403-010 Sao Paulo, SP, Brazil.
authors: Wagner F
authors: WF
authors: Gattaz
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology*; D019412:Anatomy, Cross-Sectional / Q000379:methods; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000473:pathology*; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D021621:Imaging, Three-Dimensional / Q000379:methods; D018020:Lithium Compounds / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000008:administration & dosage; D017966:Pyramidal Cells / Q000166:cytology* / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D018020:Lithium Compounds; D018696:Neuroprotective Agents
keywords: Adult brain; Alzheimer disease; CA1 region; Lithium; Neuron number; Stereology; Structural neuroplasticity