Tau underlies synaptic and cognitive deficits for type 1, but not type 2 diabetes mouse models.
Aged
Aged, 80 and over
Animals
Cognitive Dysfunction
/ metabolism
Diabetes Mellitus, Type 1
/ chemically induced
Diabetes Mellitus, Type 2
Disease Models, Animal
Female
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Obese
Mice, Transgenic
Streptozocin
Synapses
/ metabolism
tau Proteins
/ metabolism
Alzheimer’s disease
cognition
dendritic spines
diabetes mellitus
synaptic deficit
tau
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
21
09
2018
revised:
25
12
2018
accepted:
13
01
2019
pubmed:
28
2
2019
medline:
15
9
2020
entrez:
28
2
2019
Statut:
ppublish
Résumé
Diabetes mellitus (DM) is one of the most devastating diseases that currently affects the aging population. Recent evidence indicates that DM is a risk factor for many brain disorders, due to its direct effects on cognition. New findings have shown that the microtubule-associated protein tau is pathologically processed in DM; however, it remains unknown whether pathological tau modifications play a central role in the cognitive deficits associated with DM. To address this question, we used a gain-of-function and loss-of-function approach to modulate tau levels in type 1 diabetes (T1DM) and type 2 diabetes (T2DM) mouse models. Our study demonstrates that tau differentially contributes to cognitive and synaptic deficits induced by DM. On one hand, overexpressing wild-type human tau further exacerbates cognitive and synaptic impairments induced by T1DM, as human tau mice treated under T1DM conditions show robust deficits in learning and memory processes. On the other hand, neither a reduction nor increase in tau levels affects cognition in T2DM mice. Together, these results shine new light onto the different molecular mechanisms that underlie the cognitive and synaptic impairments associated with T1DM and T2DM.
Identifiants
pubmed: 30809950
doi: 10.1111/acel.12919
pmc: PMC6516168
doi:
Substances chimiques
tau Proteins
0
Streptozocin
5W494URQ81
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
e12919Subventions
Organisme : Alzheimer's Association
ID : NIRG-15-363477
Pays : International
Organisme : Larry Hillblom Foundation
ID : 2016-A-016-FEL
Pays : International
Organisme : Larry Hillblom Foundation
ID : 2013-A-016-FEL
Pays : International
Organisme : NIA NIH HHS
ID : P01 AG000538
Pays : United States
Organisme : University of California and Institute for Mexico
ID : CN-16-170
Pays : International
Organisme : BrightFocus Foundation
ID : A2015535S
Pays : International
Organisme : Alzheimer's Association
ID : AARF-16-44060
Pays : International
Organisme : Alzheimer's Association
ID : MNIRGD-15-363229
Pays : International
Organisme : National Institute of Health NIH/NIA
ID : P50 AG16573
Pays : International
Informations de copyright
© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
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