Cited by 53Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration Mechanisms

L-Stepholidine rescues memory deficit and synaptic plasticity in models of Alzheimer’s disease via activating dopamine D1 receptor/PKA signaling pathway

Open access
Hao, J-R, Sun, N, Lei, L, Li, X-Y, Yao, B, Sun, K, Hu, R, Zhang, X +2 more·2015·Cell Death & Disease

Abstract

It is accepted that amyloid β-derived diffusible ligands (ADDLs) have a prominent role in triggering the early cognitive deficits that constitute Alzheimer's disease (AD). However, there is still no effective treatment for preventing or reversing the progression of the disease. Targeting α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor trafficking and its regulation is a new strategy for AD early treatment. Here we investigate the effect and mechanism of L-Stepholidine (L-SPD), which elicits dopamine D1-type receptor agonistic activity, while acting as D2-type receptor antagonist on cognition and synaptic plasticity in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic (APP/PS1) mice, and hippocampal cultures or slices treated with ADDLs. L-SPD could improve the hippocampus-dependent memory, surface expression of glutamate receptor A (GluA1)-containing AMPA receptors and spine density in hippocampus of APP/PS1 transgenic mice. L-SPD not only rescued decreased phosphorylation and surface expression of GluA1 in hippocampal cultures but also protected the long-term potentiation in hippocampal slices induced by ADDLs. Protein kinase A (PKA) agonist Sp-cAMPS or D1-type receptor agonist SKF81297 had similar effects, whereas PKA antagonist Rp-cAMPS or D1-type receptor antagonist SCH23390 abolished the effect of L-SPD on GluA1 trafficking. This was mediated mainly by PKA, which could phosphorylate serine residue at 845 of the GluA1. L-SPD may be explored as a potential therapeutic drug for AD through a mechanism that improves AMPA receptor trafficking and synaptic plasticity via activating D1/PKA signaling pathway.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/cddis.2015.315

Cites

46 of 46 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The increase of DA drive, evoked by dopaminergic drugs or stimulation of dopaminergic neurotransmission, improves synaptic plasticity dysfunctions, cognitive impairment and memory deficits in different experimental models of AD.

    “the increase of DA drive -evoked by dopaminergic drugs or stimulation of the dopa­ minergic neurotransmission -improves synaptic plasticity dysfunctions, cognitive impairment and memory deficits in different experimental models of AD”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Hao, J.-R., Sun, N., Lei, L., Li, X.-Y., Yao, B., Sun, K., Hu, R., Zhang, X., Shi, X.-D., & Gao, C.
Affiliations
Xuzhou Medical College (CN)
Corresponding author
Gao, C
Venue
Cell Death & Disease
Published
2015-11-05
Volume
6
Issue
11
Pages
e1965-e1965
ISSN
2041-4889 (ISSN-L)
OpenAlex
W1931174500
Cited by
53
References
46
Citations by year
2026: 1 · 2025: 6 · 2024: 2 · 2023: 3 · 2022: 7 · 2021: 6 · 2020: 4 · 2019: 12 · 2018: 5 · 2017: 4 · 2016: 3
FWCI
3.19
Type
journal article
Language
en
Open access
Locations
  • Cell Death and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81300930, 81471101, BK20130232, 81273489)
  • Government of Jiangsu Province
  • Natural Science Foundation of Jiangsu Province
  • Qinglan Project of Jiangsu Province of China
  • Key University Science Research Project of Jiangsu Province
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, dopamine D1 receptor, protein kinase A signaling, AMPA receptor trafficking, GluA1 phosphorylation, APP/PS1 mice, hippocampal-dependent memory, synaptic plasticity, long-term potentiation, dopamine D2 receptor antagonists, cognitive impairment
MeSH terms
Alzheimer Disease, Animals, Berberine, Male, Memory Disorders, Mice, Transgenic, Antipsychotic Agents, Signal Transduction, Rats, Sprague-Dawley, Receptors, Dopamine D1, Cyclic AMP-Dependent Protein Kinases, Dopamine Agonists, Mice, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review