N-palmitoyl serotonin alleviates scopolamine-induced memory impairment via regulation of cholinergic and antioxidant systems, and expression of BDNF and p-CREB in mice

Min, A Young; Doo, Choon Nan; Son, Eun Jung; Sung, Nak Yun; Lee, Kun Jong; Sok, Dai‐Eun; Kim, Mee Ree

doi:10.1016/j.cbi.2015.09.016

Cited by 33 publications

(33 citation statements)

References 58 publications

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“…Morris water maze test was performed according to the method reported previously [9]. One hour before the trial, mice were administrated with NAS (1 or 30 mg/kg, p.o.).…”

Section: Methodsmentioning

confidence: 99%

“…The passive avoidance test was performed following the method reported previously [9]. One hour before the acquisition trial, mice were orally administrated with NAS prior to the administration with scopolamine.…”

Section: Methodsmentioning

confidence: 99%

“…The H&E staining assay was performed following the previous method [9]. Mice were anesthetized, and perfused with ice-cold PBS and then ice-cold 2% paraformaldehyde solution in PBS (pH 7.4).…”

Section: Methodsmentioning

confidence: 99%

“…Scopolamine (PubChem CID: 5184) is known as an antagonist of muscarinic acetylcholine receptor [4], and causing memory impairment in rodents [5], [6] and humans [7]. In addition, scopolamine induces oxidative stress in brain [8], and reduces formation of brain-derived neurotrophic factor (BDNF) in neuronal cells [9]. Therefore, administration of scopolamine for in vivo experiment is generally used as a model of memory impairment for Alzheimer's disease.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we found that N -acyl serotonins possessed properties of excellent antioxidants and neuroprotection in glutamate-treated neuronal cells [2] and scopolamine-treated mice [9]. Although N -palmitoyl serotonin at submicromolar range possessed exceptional neuroprotective properties, it was not tested clinically.…”

Section: Introductionmentioning

confidence: 99%

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Neuroprotective action of N-acetyl serotonin in oxidative stress-induced apoptosis through the activation of both TrkB/CREB/BDNF pathway and Akt/Nrf2/Antioxidant enzyme in neuronal cells

et al. 2017

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N-acetyl serotonin (NAS) as a melatonin precursor has neuroprotective actions. Nonetheless, it is not clarified how NAS protects neuronal cells against oxidative stress. Recently, we have reported that N-palmitoyl serotonins possessed properties of antioxidants and neuroprotection. Based on those, we hypothesized that NAS, a N-acyl serotonin, may have similar actions in oxidative stress-induced neuronal cells, and examined the effects of NAS based on in vitro and in vivo tests. NAS dose-dependently inhibited oxidative stress-induced cell death in HT-22 cells. Moreover, NAS suppressed glutamate-induced apoptosis by suppressing expression of AIF, Bax, calpain, cytochrome c and cleaved caspase-3, whereas it enhanced expression of Bcl-2. Additionally, NAS improved phosphorylation of tropomyosin-related kinase receptor B (TrkB) and cAMP response element-binding protein (CREB) as well as expression of brain-derived neurotrophic factor (BDNF), whereas the inclusion of each inhibitor of JNK, p38 or Akt neutralized the neuroprotective effect of NAS, but not that of ERK. Meanwhile, NAS dose-dependently reduced the level of reactive oxygen species, and enhanced the level of glutathione in glutamate-treated HT-22 cells. Moreover, NAS significantly increased expression of heme oxygenase-1, NAD(P)H quinine oxidoreductase-1 and glutamate-cysteine ligase catalytic subunit as well as nuclear translocation of NF-E2-related factor-2. Separately, NAS at 30 mg/kg suppressed scopolamine-induced memory impairment and cell death in CA1 and CA3 regions in mice. In conclusion, NAS shows actions of antioxidant and anti-apoptosis by activating TrkB/CREB/BDNF pathway and expression of antioxidant enzymes in oxidative stress-induced neurotoxicity. Therefore, such effects of NAS may provide the information for the application of NAS against neurodegenerative diseases.

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“…Morris water maze test was performed according to the method reported previously [9]. One hour before the trial, mice were administrated with NAS (1 or 30 mg/kg, p.o.).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Neuroprotective action of N-acetyl serotonin in oxidative stress-induced apoptosis through the activation of both TrkB/CREB/BDNF pathway and Akt/Nrf2/Antioxidant enzyme in neuronal cells

et al. 2017

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Anti‐Apoptotic Effect of N‐Palmitoyl Serotonin on Glutamate‐Mediated Apoptosis Through Secretion of BDNF and Activation of TrkB/CREB Pathway in HT‐22 Cells

Yoo

Lee

et al. 2017

Euro J Lipid Sci & Tech

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Recently, N‐acyl serotonins have been reported to exert neuroprotective actions against oxidative stress by inducing antioxidant enzymes. However, the mechanisms for the neuroprotective action of N‐acyl serotonins are still not clarified. In this study, we focuse on the suppressive effect of N‐palmitoyl serotonin on glutamate‐induced apoptosis in HT‐22 cells, and then examine the molecular mechanism for anti‐apoptotic action of N‐palmitoyl serotonin. For this purpose, flow cytometry, immunoblotting analysis and antibody‐mediated neutralization is formed. When HT‐22 cells are preincubated with N‐palmitoyl serotonin prior to glutamate treatment, N‐palmitoyl serotonin dose‐dependently reduces apoptotic bodies, and recoveres mitochondrial potential in glutamate‐treated HT‐22 cells. Further, N‐palmitoyl serotonin concentration‐dependently increases the expression of B‐cell lymphoma 2 (Bcl‐2), an anti‐apoptotic factor, whereas it reduces the expression of Bcl‐2‐associated X protein, apoptosis‐inducing factor, Ca2+‐dependent non‐lysosomal cysteine protease, cytochrome c, and cleaves caspase‐3. Meanwhile, N‐palmitoyl serotonin enhanced phosphorylation of tropomyosin‐related kinase receptors (TrkB) and cAMP response element‐binding protein (CREB) as well as expression of brain‐derived neurotrophic factor (BDNF). Separately, the inclusion of anti‐BDNF antibody neutralizes the neuroprotective action of N‐palmitoyl serotonin against glutamate‐induced cell death. In addition, K252a, a TrkB inhibitor, also reverses neuroprotective effect of N‐palmitoyl serotonin, suggesting that the action of N‐palmitoyl serotonin may be expressed through the formation of BDNF. Based on these results, it is proposed that N‐palmitoyl serotonin promotes formation and secretion of BDNF, and then protects neuronal cells against oxidative stress‐induced apoptosis through activation of TrkB/CREB pathway. Practical Applications: The results may provide further information for the application of N‐acyl serotonins as a therapeutic or preventive agent for neurodegenerative diseases. N‐Palmitoyl 2 serotonin (Pal‐5HT) not only induces brain‐derived neurotrophic factor (BDNF) expression but also protects neuronal cells against oxidative stress.

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Docosahexaenoyl serotonin, an endogenously formed n-3 fatty acid-serotonin conjugate has anti-inflammatory properties by attenuating IL-23–IL-17 signaling in macrophages

Poland

Klooster

Wang

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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N-palmitoyl serotonin alleviates scopolamine-induced memory impairment via regulation of cholinergic and antioxidant systems, and expression of BDNF and p-CREB in mice

Cited by 33 publications

References 58 publications

Neuroprotective action of N-acetyl serotonin in oxidative stress-induced apoptosis through the activation of both TrkB/CREB/BDNF pathway and Akt/Nrf2/Antioxidant enzyme in neuronal cells

Neuroprotective action of N-acetyl serotonin in oxidative stress-induced apoptosis through the activation of both TrkB/CREB/BDNF pathway and Akt/Nrf2/Antioxidant enzyme in neuronal cells

Anti‐Apoptotic Effect of N‐Palmitoyl Serotonin on Glutamate‐Mediated Apoptosis Through Secretion of BDNF and Activation of TrkB/CREB Pathway in HT‐22 Cells

Docosahexaenoyl serotonin, an endogenously formed n-3 fatty acid-serotonin conjugate has anti-inflammatory properties by attenuating IL-23–IL-17 signaling in macrophages

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