ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2000
Positive modulation of AMPA receptors increases neurotrophin expression by hippocampal and cortical neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
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Who cites it
100 citing papers in PubMed, 2 syntheses or guidelines pooled it, 288 citations in OpenAlex.
- Research Progress on the Antidepressant Effects of Baicalin and Its Aglycone Baicalein: A Systematic Review of the Biological Mechanisms.Neurochemical research · 2024Pooled it
- Pooled it
- Trial
- AMPA receptor modulation in depression: from molecular mechanisms of plasticity to therapeutic translation.Pharmacological reports : PR · 2026Review
- Acute Administration of Ampakine CX1739 after Cervical Spinal Cord Injury.Journal of neurotrauma · 2026Article
- Oligomeric alpha-synuclein causes early synaptic dysfunction of the corticostriatal pathway associated with non-motor symptoms.NPJ Parkinson's disease · 2025Article
- Positive AMPA and Kainate Receptor Modulators and Their Therapeutic Potential in CNS Diseases: A Comprehensive Review.International journal of molecular sciences · 2025Review
- Pharmacological modulation of respiratory control: Ampakines as a therapeutic strategy.Pharmacology & therapeutics · 2025Review
- AMPA receptors play an important role in the biological consequences of spinal cord injury: Implications for AMPA receptor modulators for therapeutic benefit.Biochemical pharmacology · 2024Review
- Cisplatin induces BDNF downregulation in middle-aged female rat model while BDNF enhancement attenuates cisplatin neurotoxicity.Experimental neurology · 2024Article
- Preclinical Pharmacology of CX1837, a High-Impact Ampakine with an Improved Safety Margin: Implications for Treating Alzheimer's Disease and Ischemic Stroke.Current Alzheimer research · 2024Article
- Preclinical characterization of a water-soluble low-impact ampakine prodrug, CX1942 and its active moiety, CX1763.Future medicinal chemistry · 2024Article
- Targeting synapse function and loss for treatment of neurodegenerative diseases.Nature reviews. Drug discovery · 2024Review
- Ketamine and the neurobiology of depression: Toward next-generation rapid-acting antidepressant treatments.Proceedings of the National Academy of Sciences of the United States of America · 2023Review
- St. John's wort (Hypericum perforatum) and depression: what happens to the neurotransmitter systems?Naunyn-Schmiedeberg's archives of pharmacology · 2022Review
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- Review
- Glutamate and depression: Reflecting a deepening knowledge of the gut and brain effects of a ubiquitous molecule.World journal of psychiatry · 2021Review
- Strictly regulated agonist-dependent activation of AMPA-R is the key characteristic of TAK-653 for robust synaptic responses and cognitive improvement.Scientific reports · 2021Article
- Ketamine-50 years in use: from anesthesia to rapid antidepressant effects and neurobiological mechanisms.Pharmacological reports : PR · 2021Review
40 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
This study investigated whether positive modulators of AMPA-type glutamate receptors influence neurotrophin expression by forebrain neurons. Treatments with the ampakine CX614 markedly and reversibly increased brain-derived neurotrophic factor (BDNF) mRNA and protein levels in cultured rat entorhinal/hippocampal slices. Acute effects of CX614 were dose dependent over the range in which the drug increased synchronous neuronal discharges; threshold concentrations for acute responses had large effects on mRNA content when applied for 3 d. Comparable results were obtained with a second, structurally distinct ampakine CX546. Ampakine-induced upregulation was broadly suppressed by AMPA, but not NMDA, receptor antagonists and by reducing transmitter release. Antagonism of L-type voltage-sensitive calcium channels blocked induction in entorhinal cortex but not hippocampus. Prolonged infusions of suprathreshold ampakine concentrations produced peak BDNF mRNA levels at 12 hr and a return to baseline levels by 48 hr. In contrast, BDNF protein remained elevated throughout a 48 hr incubation with the drug. Nerve growth factor mRNA levels also were increased by ampakines but with a much more rapid return to control levels during chronic administration. Finally, intraperitoneal injections of CX546 increased hippocampal BDNF mRNA levels in aged rats and middle-aged mice. The present results provide evidence of regional differences in mechanisms via which activity regulates neurotrophin expression. Moreover, these data establish that changes in synaptic potency produce sufficient network level physiological effects for inducing neurotrophin genes, indicate that the response becomes refractory during prolonged ampakine exposure, and raise the possibility of using positive AMPA modulators to regulate neurotrophin levels in aged brain.
Indexed as
Identifiers
10627576PMC6774091W1780394705What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.