ArticleMolecular neurobiology2016
Subthreshold Concentrations of Melatonin and Galantamine Improves Pathological AD-Hallmarks in Hippocampal Organotypic Cultures.
Article in Molecular neurobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Neuroprotective Activity of 3-((6-(Phenylethynyl)pyridin-3-yl)oxy)quinuclidine: A Potential Ligand for the Treatment of Alzheimer's Disease.ACS chemical neuroscience · 2025Article
- Protective Activity of Melatonin Combinations and Melatonin-Based Hybrid Molecules in Neurodegenerative Diseases.Journal of pineal research · 2024Review
- The protective effects of melatonin in high glucose environment by alleviating autophagy and apoptosis on primary cortical neurons.Molecular and cellular biochemistry · 2023Article
- Influence of galantamine on peripheral nerve degeneration after experimental compression injury of the rat sciatic nerve.Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery : TJTES · 2022Article
- Protective effect ofFrontiers in pharmacology · 2022Article
- Neuroprotective Effects of Cholinesterase Inhibitors: Current Scenario in Therapies for Alzheimer's Disease and Future Perspectives.Journal of Alzheimer's disease reports · 2022Review
- Implications of Oligomeric Amyloid-Beta (oAβThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Melatonin Rescues the Dendrite Collapse Induced by the Pro-Oxidant Toxin Okadaic Acid in Organotypic Cultures of Rat Hilar Hippocampus.Molecules (Basel, Switzerland) · 2020Article
- Copper Toxicity Links to Pathogenesis of Alzheimer's Disease and Therapeutics Approaches.International journal of molecular sciences · 2020Review
- Neuroprotective effects of EpoL against oxidative stress induced by soluble oligomers of Aβ peptide.Redox biology · 2019Article
- Human Brain Slice Culture: A Useful Tool to Study Brain Disorders and Potential Therapeutic Compounds.Neuroscience bulletin · 2019Review
- NRF2 and NF-қB interplay in cerebrovascular and neurodegenerative disorders: Molecular mechanisms and possible therapeutic approaches.Redox biology · 2019Review
- Modulation of serine/threonine phosphatases by melatonin: therapeutic approaches in neurodegenerative diseases.British journal of pharmacology · 2018Review
- Neuroprotective effects of erythropoietin on neurodegenerative and ischemic brain diseases: the role of erythropoietin receptor.Neural regeneration research · 2017Review
- Galantamine and Environmental Enrichment Enhance Cognitive Recovery after Experimental Traumatic Brain Injury But Do Not Confer Additional Benefits When Combined.Journal of neurotrauma · 2017Article
- Serum Copper, Zinc, and Iron Levels in Patients with Alzheimer's Disease: A Meta-Analysis of Case-Control Studies.Frontiers in aging neuroscience · 2017Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Melatonin is a neurohormone whose levels are significantly reduced or absent in Alzheimer's disease (AD) patients. In these patients, acetylcholinesterase inhibitors (AChEI) are the major drug class used for their treatment; however, they present unwanted cholinergic side effects and have provided limited efficacy in clinic. Because combination therapy is being extensively used to treat different pathological diseases such as cancer or acquired immune deficiency syndrome, we posed this study to evaluate if melatonin in combination with an AChEI, galantamine, could provide beneficial properties in a novel in vitro model of AD. Thus, we subjected organotypic hippocampal cultures (OHCs) to subtoxic concentrations of β-amyloid (0.5 μM βA) plus okadaic acid (1 nM OA), for 4 days. This treatment increased by 95 % cell death, which was mainly apoptotic as shown by positive TUNEL staining. In addition, the combination of βA/OA increased Thioflavin S aggregates, hyperphosphorylation of Tau, oxidative stress (increased DCFDA fluorescence), and neuroinflammation (increased IL-1β and TNFα). Under these experimental conditions, melatonin (1-1000 nM) and galantamine (10-1000 nM), co-incubated with the toxic stimuli, caused a concentration-dependent neuroprotection; maximal neuroprotective effect was achieved at 1 μM of melatonin and galantamine. Most effective was the finding that combination of sub-effective concentrations of melatonin (1 nM) and galantamine (10 nM) provided a synergic anti-apoptotic effect and reduction of most of the AD-related pathological hallmarks observed in the βA/OA model. Therefore, we suggest that supplementation of melatonin in combination with lower doses of AChEIs could be an interesting strategy for AD patients.
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