Effects of Reducing Norepinephrine Levels via DSP4 Treatment on Amyloid-β Pathology in Female Rhesus Macaques (Macaca Mulatta)
| Autor: | Julie A. Mattison, Richard Herbert, Balmiki Ray, Debomoy K. Lahiri, Gregory P. Tinkler, Mary Ann Ottinger, Edward M. Tilmont, Nigel H. Greig, Donald K. Ingram, Kara B. Duffy |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Benzylamines Amyloid Article 03 medical and health sciences Norepinephrine Amyloid beta-Protein Precursor Random Allocation 0302 clinical medicine Dopamine Internal medicine Medicine Neurotoxin Animals Neurotransmitter Uptake Inhibitors Neuroinflammation Amyloid beta-Peptides Microglia business.industry General Neuroscience General Medicine Macaca mulatta Peptide Fragments Psychiatry and Mental health Clinical Psychology 030104 developmental biology medicine.anatomical_structure Endocrinology Immunohistochemistry Locus coeruleus Female Locus Coeruleus Geriatrics and Gerontology business 030217 neurology & neurosurgery medicine.drug |
| Popis: | The degeneration in the locus coeruleus associated with Alzheimer’s disease suggests an involvement of the noradrenergic system in the disease pathogenesis. The role of depleted norepinephrine was tested in adult and aged rhesus macaques to develop a potential model for testing Alzheimer’s disease interventions. Monkeys were injected with the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) or vehicle at 0, 3, and 6 months; brains were harvested at 9 months. Reduced norepinephrine in the locus coeruleus was accompanied by decreased dopamine β-hydroxylase staining and increased amyloid-β load in the aged group, and the proportion of potentially toxic amyloid-β(42) peptide was increased. Immunohistochemistry revealed no effects on microglia or astrocytes. DSP4 treatment altered amyloid processing, but these changes were not associated with the induction of chronic neuroinflammation. These findings suggest norepinephrine deregulation is an essential component of a nonhuman primate model of Alzheimer’s disease, but further refinement is necessary. |
| Databáze: | OpenAIRE |
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