ArticleCell death & disease2015
L-Stepholidine rescues memory deficit and synaptic plasticity in models of Alzheimer's disease via activating dopamine D1 receptor/PKA signaling pathway.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- Article
- Optogenetic stimulation of midbrain dopaminergic neurons rescues hippocampal synaptic plasticity deficits in a mouse model of Alzheimer's disease.Translational psychiatry · 2025Article
- PF-04691502, a PI3K/mTOR Dual Inhibitor, Ameliorates AD-like Pathology in a Mouse Model of AD.Cells · 2025Article
- Repetitive prefrontal tDCS activates VTA dopaminergic neurons, resulting in attenuation of Alzheimer's Disease-like deficits in Tg2576 mice.Alzheimer's research & therapy · 2025Article
- An Expanded Narrative Review of Neurotransmitters on Alzheimer's Disease: The Role of Therapeutic Interventions on Neurotransmission.Molecular neurobiology · 2025Review
- Levo-Stepholidine as a Potential Cognitive Enhancer: Insights into Executive Function and Memory Improvements.Biomedicines · 2024Article
- Long-term potentiation-based screening identifies neuronal PYGM as a synaptic plasticity regulator participating in Alzheimer's disease.Zoological research · 2023Article
- Therapeutic Strategies Aimed at Improving Neuroplasticity in Alzheimer Disease.Pharmaceutics · 2023Review
- The Effects of Ninjinyoeito on Impaired Spatial Memory and Prefrontal Cortical Synaptic Plasticity throughEvidence-based complementary and alternative medicine : eCAM · 2023Article
- Article
- The VTA dopaminergic system as diagnostic and therapeutical target for Alzheimer's disease.Frontiers in psychiatry · 2022Article
- Forsythoside A Mitigates Alzheimer's-like Pathology by Inhibiting Ferroptosis-mediated Neuroinflammation via Nrf2/GPX4 Axis Activation.International journal of biological sciences · 2022Article
- Understanding How Physical Exercise Improves Alzheimer's Disease: Cholinergic and Monoaminergic Systems.Frontiers in aging neuroscience · 2022Review
- Sex Differences in Dopamine Receptor Signaling inBrain sciences · 2021Article
- Active-Ingredient Screening and Synergistic Action Mechanism of Shegan Mixture for Anti-Asthma Effects Based on Network Pharmacology in a Mouse Model of Asthma.Drug design, development and therapy · 2021Article
- The Role of Chinese Herbal Therapy in Methamphetamine Abuse and its Induced Psychiatric Symptoms.Frontiers in pharmacology · 2021Review
- Acetylation of AMPA Receptors Regulates Receptor Trafficking and Rescues Memory Deficits in Alzheimer's Disease.iScience · 2020Article
- A critical review: traditional uses, phytochemistry, pharmacology and toxicology ofPhytochemistry reviews : proceedings of the Phytochemical Society of Europe · 2020Review
- Differences in DNA Methylation Reprogramming Underlie the Sexual Dimorphism of Behavioral Disorder Caused by Prenatal Stress in Rats.Frontiers in neuroscience · 2020Article
- HDAC2 hyperexpression alters hippocampal neuronal transcription and microglial activity in neuroinflammation-induced cognitive dysfunction.Journal of neuroinflammation · 2019Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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