1. Aβ dimers induce behavioral and neurochemical deficits of relevance to early Alzheimer's disease
- Author
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Benedetta Fazari, Susanne Nikolaus, Maria A. de Souza Silva, Valéria Lamounier-Zepter, Arne Herring, Laila Abdel-Hafiz, Andreas Müller-Schiffmann, Joseph P. Huston, Carsten Korth, Sandra Schäble, Owen Y. Chao, and Kathy Keyvani
- Subjects
Male ,0301 basic medicine ,Serotonin ,Aging ,Amyloid beta ,Dopamine ,Medizin ,Hippocampus ,Mice, Transgenic ,Hippocampal formation ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Neurochemical ,Alzheimer Disease ,Animals ,Medicine ,Neurotransmitter ,Brain Chemistry ,Amyloid beta-Peptides ,Behavior, Animal ,biology ,business.industry ,General Neuroscience ,Ventral striatum ,Brain ,Hydroxyindoleacetic Acid ,Entorhinal cortex ,Acetylcholine ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,biology.protein ,3,4-Dihydroxyphenylacetic Acid ,Neurology (clinical) ,Geriatrics and Gerontology ,business ,Neuroscience ,Stress, Psychological ,030217 neurology & neurosurgery ,Developmental Biology ,medicine.drug - Abstract
We examined behaviors and neurotransmitter levels in the tgDimer mouse, a model for early Alzheimer's disease, that expresses exclusively soluble amyloid beta (Aβ) dimers and is devoid of Aβ plaques, astrogliosis, and neuroinflammation. Seven-month-old mice were subjected to tests of motor activity, attention, anxiety, habituation learning, working memory, and depression-related behaviors. They were impaired in nonselective attention and motor learning and showed anxiety- and despair-related behaviors. In 7- and 12-month-old mice, levels of acetylcholine, dopamine, and serotonin were measured in neostriatum, ventral striatum, prefrontal cortex, hippocampus, amygdala, and entorhinal cortex by high-performance liquid chromatography. The tgDimer mice had lower serotonin turnover rates in hippocampus, ventral striatum, and amygdala relative to wild type controls. The aged tgDimer mice had less hippocampal acetylcholine than adult tgDimers. Stress-test results, based on corticosterone levels, indicated an intact hypothalamus-pituitary-adrenal axis in 12-month-old mice. Since neither Aβ plaques nor astrogliosis or neuroinflammation was responsible for these phenotypes, we conclude that Aβ dimers contribute to neurotransmitter dysfunction and behavioral impairments, characteristic for the early stages of Alzheimer's disease.
- Published
- 2018