Age-related calcium dysregulation linked with tau pathology and impaired cognition in non-human primates.

Aging / pathology Animals Calcium / metabolism Calcium Signaling Cognitive Dysfunction / pathology Cyclic AMP-Dependent Protein Kinases / metabolism Disease Models, Animal Humans Macaca mulatta Male Neurons / metabolism Phosphorylation Prefrontal Cortex / pathology Rats Ryanodine Receptor Calcium Release Channel tau Proteins / metabolism
PKA aging association cortex calpain impaired cognition macaque pyramidal cells ryanodine receptor tau

Journal

Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978

Informations de publication

Date de publication:
06 2021
Historique:
revised: 04 02 2021
received: 24 08 2020
accepted: 11 02 2021
pubmed: 9 4 2021
medline: 16 11 2021
entrez: 8 4 2021
Statut: ppublish

Résumé

The etiology of sporadic Alzheimer's disease (AD) requires non-genetically modified animal models. The relationship of tau phosphorylation to calcium-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) dysregulation was analyzed in aging rhesus macaque dorsolateral prefrontal cortex (dlPFC) and rat primary cortical neurons using biochemistry and immuno-electron microscopy. The influence of calcium leak from ryanodine receptors (RyRs) on neuronal firing and cognitive performance was examined in aged macaques. Aged monkeys naturally develop hyperphosphorylated tau, including AD biomarkers (AT8 (pS202/pT205) and pT217) and early tau pathology markers (pS214 and pS356) that correlated with evidence of increased calcium leak (pS2808-RyR2). Calcium also regulated early tau phosphorylation in vitro. Age-related reductions in the calcium-binding protein, calbindin, and in phosphodiesterase PDE4D were seen within dlPFC pyramidal cell dendrites. Blocking RyRs with S107 improved neuronal firing and cognitive performance in aged macaques. Dysregulated calcium signaling confers risk for tau pathology and provides a potential therapeutic target.

Identifiants

DOI: 10.1002/alz.12325 PMID: 33829643 PMC: PMC8195842
pubmed: 33829643
doi: 10.1002/alz.12325
pmc: PMC8195842
mid: NIHMS1678459
doi:

Substances chimiques

Ryanodine Receptor Calcium Release Channel 0
tau Proteins 0
Cyclic AMP-Dependent Protein Kinases EC 2.7.11.11
Calcium SY7Q814VUP

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

920-932

Subventions

Organisme : NIA NIH HHS
ID : R01 AG061190
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG052986
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG047270
Pays : United States
Organisme : NIA NIH HHS
ID : DP1 AG047744
Pays : United States
Organisme : NIA NIH HHS
ID : F31 AG063425
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA023999
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH113257
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG052986
Pays : United States
Organisme : NINDS NIH HHS
ID : T32 NS041228
Pays : United States
Organisme : NIDA NIH HHS
ID : R37 DA023999
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066508
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG062306
Pays : United States

Informations de copyright

© 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

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Auteurs

Dibyadeep Datta (D)

Departments of Neuroscience, School of Medicine, Yale University, Connecticut, USA.

Shannon N Leslie (SN)

Department of Psychiatry, School of Medicine, Yale University, Connecticut, USA.
Interdepartmental Neuroscience Program, School of Medicine, Yale University, Connecticut, USA.

Min Wang (M)

Departments of Neuroscience, School of Medicine, Yale University, Connecticut, USA.

Yury M Morozov (YM)

Departments of Neuroscience, School of Medicine, Yale University, Connecticut, USA.

Shengtao Yang (S)

Departments of Neuroscience, School of Medicine, Yale University, Connecticut, USA.

SueAnn Mentone (S)

Departments of Neuroscience, School of Medicine, Yale University, Connecticut, USA.

Caroline Zeiss (C)

Department of Comparative Medicine, School of Medicine, Yale University, Connecticut, USA.

Alvaro Duque (A)

Departments of Neuroscience, School of Medicine, Yale University, Connecticut, USA.

Pasko Rakic (P)

Departments of Neuroscience, School of Medicine, Yale University, Connecticut, USA.

Tamas L Horvath (TL)

Department of Comparative Medicine, School of Medicine, Yale University, Connecticut, USA.

Christopher H van Dyck (CH)

Departments of Neuroscience, School of Medicine, Yale University, Connecticut, USA.
Department of Psychiatry, School of Medicine, Yale University, Connecticut, USA.

Angus C Nairn (AC)

Department of Psychiatry, School of Medicine, Yale University, Connecticut, USA.

Amy F T Arnsten (AFT)

Departments of Neuroscience, School of Medicine, Yale University, Connecticut, USA.

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Classifications MeSH

questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Vieillissement › Age-related calcium dysregulation linked with...
questionsmedicales.fr › Eucaryotes › Animaux › Age-related calcium dysregulation linked with...
questionsmedicales.fr › Facteurs biologiques › Facteurs de la coagulation sanguine › Calcium › Age-related calcium dysregulation linked with...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Systèmes de seconds messagers › Signalisation calcique › Age-related calcium dysregulation linked with...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Troubles de la cognition › Dysfonctionnement cognitif › Age-related calcium dysregulation linked with...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Cyclic Nucleotide-Regulated Protein Kinases › Cyclic AMP-Dependent Protein Kinases › Age-related calcium dysregulation linked with...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Age-related calcium dysregulation linked with...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Age-related calcium dysregulation linked with...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Cercopithecidae › Cercopithecinae › Macaca › Macaca mulatta › Age-related calcium dysregulation linked with...
questionsmedicales.fr › Cellules › Neurones › Age-related calcium dysregulation linked with...
questionsmedicales.fr › Métabolisme › Phosphorylation › Age-related calcium dysregulation linked with...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Cortex cérébral › Lobe frontal › Cortex préfrontal › Age-related calcium dysregulation linked with...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Age-related calcium dysregulation linked with...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Canaux ioniques › Canaux calciques › Canal de libération du calcium du récepteur à la ryanodine › Age-related calcium dysregulation linked with...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines associées aux microtubules › Protéines tau › Age-related calcium dysregulation linked with...