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Chronic over-expression of ubiquitin impairs learning, reduces synaptic plasticity, and enhances GRIA receptor turnover in mice.

Journal of neurochemistry | 2019

Ubiquitin is an essential signaling protein that controls many different cellular processes. While cellular ubiquitin levels normally cycle between pools of free and conjugated ubiquitin, the balance of these ubiquitin pools can be shifted by exposure to a variety of cellular stresses. Altered ubiquitin pools are also observed in several neurological disorders, suggesting that imbalances in ubiquitin homeostasis may contribute to neuronal dysfunction. To examine the effects of increased ubiquitin levels on the mammalian nervous system, we generated transgenic mice that express ubiquitin under the control of the Thy1.2 promoter. While we did not detect global changes in levels of ubiquitin conjugates in the hippocampus, we found that increasing ubiquitin levels reduced AMPA (GRIA1-4) receptor expression without affecting the levels of NMDA (GRIN) or GABAA receptors. Ubiquitin over-expression also negatively impacted hippocampus-dependent learning and memory as well as baseline excitability and synaptic plasticity at hippocampal CA3-CA1 synapses. These changes occurred in a dose-dependent manner in that mice with the highest levels of ubiquitin over-expression had the greatest deficits in synaptic function and were the most impaired in the learning and memory tasks. As chronic elevation of ubiquitin expression in neurons is sufficient to cause changes in synaptic function and cognition, altered ubiquitin homeostasis may be an important contributor to the stress-induced changes observed in neurological disorders.

Pubmed ID: 30451289 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.


AMPA Receptor (GluR 4) (D41A11) XP Rabbit mAb (antibody)

RRID:AB_10829469

This monoclonal targets AMPA Receptor (GluR 4) (D41A11) XP Rabbit mAb

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NMDAepsilon1 (H-54) (antibody)

RRID:AB_670228

This polyclonal targets GRIN2A

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TRAF3 (C-20) (antibody)

RRID:AB_2272378

This polyclonal targets TRAF3

View all literature mentions

Human Cyclin D1 MAb (Clone 328303) (antibody)

RRID:AB_2259637

This monoclonal targets Human Cyclin D1 MAb (Clone 328303)

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Bassoon, mAb (SAP7F407) (antibody)

RRID:AB_10618753

This monoclonal targets Bassoon mAb (SAP7F407)

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VPS28 (B-2) (antibody)

RRID:AB_10990105

This monoclonal targets VPS28 (B-2)

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AMPA Receptor (GluR 3) (D25G9) Rabbit mAb (antibody)

RRID:AB_10544796

This monoclonal targets AMPA Receptor (GluR 3) (D25G9) Rabbit mAb

View all literature mentions

Anti-PSD-95 Antibody (antibody)

RRID:AB_10698024

This monoclonal targets PSD-95 MAGUK scaffolding protein

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Hrs (M-79) (antibody)

RRID:AB_2264138

This polyclonal targets HGS

View all literature mentions

Anti-GluA2/GluR2 Glutamate Receptor Antibody (antibody)

RRID:AB_2232661

This monoclonal targets GluA2/GluR2 glutamate receptor

View all literature mentions

SNAP25 antibody (antibody)

RRID:AB_2192054

This polyclonal targets SNAP25

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GluR-1 (C-19) (antibody)

RRID:AB_641039

This polyclonal targets GRIA1

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NEDD4-1 (H-135) (antibody)

RRID:AB_2149316

This polyclonal targets NEDD4-1 (H-135)

View all literature mentions

tsg 101 (M-19) (antibody)

RRID:AB_2208099

This polyclonal targets TSG101

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SYT (S-13) (antibody)

RRID:AB_2239865

This polyclonal targets SS18

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Anti-GAPDH Antibody (G-9) (antibody)

RRID:AB_10847862

This monoclonal targets GAPDH

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Goat Anti-Mouse Ig (H+L) HRP (antibody)

RRID:AB_2728714

This polyclonal targets Ig (H+L)

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UCH-L5 (C-4) (antibody)

RRID:AB_10612025

This monoclonal targets UCH-L5 (C-4)

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E6-AP (H-182) (antibody)

RRID:AB_639982

This polyclonal targets UBE3A

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Anti-Synphilin-1, a.a. 829-847 (antibody)

RRID:AB_2255115

This polyclonal targets Synphilin-1, aa829-847 hsynclein alpha

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Synaptophysin antibody [EP1098Y] (antibody)

RRID:AB_882786

This monoclonal targets Synaptophysin

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Goat Anti-Rabbit Ig, Human ads-HRP (antibody)

RRID:AB_2632593

This polyclonal targets rabbit IgG

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TRAF6 (D-10) (antibody)

RRID:AB_628391

This monoclonal targets TRAF6

View all literature mentions

SNAP25 antibody (antibody)

RRID:AB_2192054

This polyclonal targets SNAP25

View all literature mentions

Anti-GAPDH Antibody (G-9) (antibody)

RRID:AB_10847862

This monoclonal targets GAPDH

View all literature mentions

Anti-PSD-95 Antibody (antibody)

RRID:AB_10698024

This monoclonal targets PSD-95 MAGUK scaffolding protein

View all literature mentions

Goat Anti-Rabbit Ig, Human ads-HRP (antibody)

RRID:AB_2632593

This polyclonal targets rabbit IgG

View all literature mentions

SYT (S-13) (antibody)

RRID:AB_2239865

This polyclonal targets SS18

View all literature mentions

Bassoon, mAb (SAP7F407) (antibody)

RRID:AB_10618753

This monoclonal targets Bassoon mAb (SAP7F407)

View all literature mentions

Anti-Synphilin-1, a.a. 829-847 (antibody)

RRID:AB_2255115

This polyclonal targets Synphilin-1, aa829-847 hsynclein alpha

View all literature mentions

Synaptophysin antibody [EP1098Y] (antibody)

RRID:AB_882786

This monoclonal targets Synaptophysin

View all literature mentions

Goat Anti-Mouse Ig (H+L) HRP (antibody)

RRID:AB_2728714

This polyclonal targets Ig (H+L)

View all literature mentions

AMPA Receptor (GluR 4) (D41A11) XP Rabbit mAb (antibody)

RRID:AB_10829469

This monoclonal targets AMPA Receptor (GluR 4) (D41A11) XP Rabbit mAb

View all literature mentions

AMPA Receptor (GluR 3) (D25G9) Rabbit mAb (antibody)

RRID:AB_10544796

This monoclonal targets AMPA Receptor (GluR 3) (D25G9) Rabbit mAb

View all literature mentions

Anti-GluA2/GluR2 Glutamate Receptor Antibody (antibody)

RRID:AB_2232661

This monoclonal targets GluA2/GluR2 glutamate receptor

View all literature mentions

GluR-1 (C-19) (antibody)

RRID:AB_641039

This polyclonal targets GRIA1

View all literature mentions

Hrs (M-79) (antibody)

RRID:AB_2264138

This polyclonal targets HGS

View all literature mentions

VPS28 (B-2) (antibody)

RRID:AB_10990105

This monoclonal targets VPS28 (B-2)

View all literature mentions

tsg 101 (M-19) (antibody)

RRID:AB_2208099

This polyclonal targets TSG101

View all literature mentions

UCH-L5 (C-4) (antibody)

RRID:AB_10612025

This monoclonal targets UCH-L5 (C-4)

View all literature mentions

TRAF3 (C-20) (antibody)

RRID:AB_2272378

This polyclonal targets TRAF3

View all literature mentions

TRAF6 (D-10) (antibody)

RRID:AB_628391

This monoclonal targets TRAF6

View all literature mentions

NMDAepsilon1 (H-54) (antibody)

RRID:AB_670228

This polyclonal targets GRIN2A

View all literature mentions

E6-AP (H-182) (antibody)

RRID:AB_639982

This polyclonal targets UBE3A

View all literature mentions

Human Cyclin D1 MAb (Clone 328303) (antibody)

RRID:AB_2259637

This monoclonal targets Human Cyclin D1 MAb (Clone 328303)

View all literature mentions

NEDD4-1 (H-135) (antibody)

RRID:AB_2149316

This polyclonal targets NEDD4-1 (H-135)

View all literature mentions