Effects of Reducing Norepinephrine Levels via DSP4 Treatment on Amyloid-β Pathology in Female Rhesus Macaques (Macaca Mulatta).

Amyloid beta-Peptides / antagonists & inhibitors Amyloid beta-Protein Precursor / antagonists & inhibitors Animals Benzylamines / pharmacology Female Locus Coeruleus / drug effects Macaca mulatta Neurotransmitter Uptake Inhibitors / pharmacology Norepinephrine / antagonists & inhibitors Peptide Fragments / antagonists & inhibitors Random Allocation
Alzheimer’s disease DSP4 locus coeruleus neurotoxin nonhuman primate norepinephrine

Journal

Journal of Alzheimer's disease : JAD
ISSN: 1875-8908
Titre abrégé: J Alzheimers Dis
Pays: Netherlands
ID NLM: 9814863

Informations de publication

Date de publication:
2019
Historique:
pubmed: 29 1 2019
medline: 19 6 2020
entrez: 29 1 2019
Statut: ppublish

Résumé

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-β42 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.

Identifiants

DOI: 10.3233/JAD-180487 PMID: 30689563 PMC: PMC6710827
pubmed: 30689563
pii: JAD180487
doi: 10.3233/JAD-180487
pmc: PMC6710827
mid: NIHMS1031319
doi:

Substances chimiques

Amyloid beta-Peptides 0
Amyloid beta-Protein Precursor 0
Benzylamines 0
Neurotransmitter Uptake Inhibitors 0
Peptide Fragments 0
amyloid beta-protein (1-42) 0
DSP 4 PQ1P7JP5C1
Norepinephrine X4W3ENH1CV

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

115-126

Subventions

Organisme : NIA NIH HHS
ID : R21 AG031387
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG018884
Pays : United States
Organisme : Intramural NIH HHS
ID : Z99 AG999999
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG042804
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG018379
Pays : United States

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Auteurs

Kara B Duffy (KB)

Animal and Avian Sciences Department, University of Maryland, College Park, MD, USA.

Balmiki Ray (B)

Myriad Neuroscience (Assurex Health), Mason, OH, USA (present address).
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.

Debomoy K Lahiri (DK)

Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.

Edward M Tilmont (EM)

Translational Gerontology Branch, National Institute on Aging, NIH Animal Center, Dickerson, MD, USA.

Gregory P Tinkler (GP)

Department of Biological Sciences, Kent State University, Kent, OH, USA.

Richard L Herbert (RL)

Clinical Medicine Branch, National Institute of Allergy and Infectious Disease, NIH, Dickerson, MD, USA.

Nigel H Greig (NH)

Translational Gerontology Branch, NIA/NIH, Baltimore, MD, USA.

Donald K Ingram (DK)

Nutritional Neuroscience and Aging Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.

Mary Ann Ottinger (MA)

Animal and Avian Sciences Department, University of Maryland, College Park, MD, USA.
Department of Biology and Biochemistry, University of Houston, Houston, TX, USA (present address).

Julie A Mattison (JA)

Translational Gerontology Branch, National Institute on Aging, NIH Animal Center, Dickerson, MD, USA.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Peptides bêta-amyloïdes › Effects of Reducing Norepinephrine Levels via...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines sécrétoires inhibitrices de protéinases › Protéase nexines › Précurseur de la protéine bêta-amyloïde › Effects of Reducing Norepinephrine Levels via...
questionsmedicales.fr › Eucaryotes › Animaux › Effects of Reducing Norepinephrine Levels via...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures cycliques › Hydrocarbures aromatiques › Dérivés du benzène › Composés benzyliques › Benzylamines › Effects of Reducing Norepinephrine Levels via...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Tronc cérébral › Rhombencéphale › Métencéphale › Pont › Tegmentum pontin › Locus ceruleus › Effects of Reducing Norepinephrine Levels via...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Cercopithecidae › Cercopithecinae › Macaca › Macaca mulatta › Effects of Reducing Norepinephrine Levels via...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Agents neuromédiateurs › Inhibiteurs de la capture des neurotransmetteurs › Effects of Reducing Norepinephrine Levels via...
questionsmedicales.fr › Composés chimiques organiques › Hydrocarbures › Hydrocarbures cycliques › Hydrocarbures aromatiques › Dérivés du benzène › Phénols › Catéchols › Catécholamines › Norépinéphrine › Effects of Reducing Norepinephrine Levels via...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Fragments peptidiques › Effects of Reducing Norepinephrine Levels via...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Répartition aléatoire › Effects of Reducing Norepinephrine Levels via...