Phlorotannin Supplement Improves Scopolamine-Induced Memory Dysfunction by Rescuing Synaptic Damage in Mice
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This study investigated the efficacy of a phlorotannin supplement (PS) in ameliorating scopolamine (SCO)-induced memory deficits in mice, focusing on synaptic function and the underlying molecular mechanisms. Male C57BL/6N mice were divided into six groups and treated with vehicle, donepezil (5 mg/kg body weight, (BW)), or PS (100, 250, or 500 mg/kg BW) for 6 weeks. Behavioral tests were conducted, followed by Golgi staining, immunofluorescence, and immunoblotting to assess synaptic protein expression and signaling pathways. Behavioral tests showed that PS administration significantly improved SCO-induced memory impairment and restored synaptic protein expression (synaptophysin, synapsin1, and postsynaptic density protein 95) in the hippocampus. Additionally, PS enhanced brain-derived neurotrophic factor (BDNF) signaling and activated the extracellular signal-regulated kinase/CAMP response element binding protein (ERK-CREB) pathway, essential for synaptic plasticity. Our findings demonstrate that PS mitigates SCO-induced memory dysfunction by protecting synaptic integrity and activating the BDNF-ERK-CREB signaling pathway, indicating the potential of PS as a natural intervention for treating memory deficits.
Abstract
This study investigated the efficacy of a phlorotannin supplement (PS) in ameliorating scopolamine (SCO)-induced memory deficits in mice, focusing on synaptic function and the underlying molecular mechanisms. Male C57BL/6N mice were divided into six groups and treated with vehicle, donepezil (5 mg/kg body weight, (BW)), or PS (100, 250, or 500 mg/kg BW) for 6 weeks. Behavioral tests were conducted, followed by Golgi staining, immunofluorescence, and immunoblotting to assess synaptic protein expression and signaling pathways. Behavioral tests showed that PS administration significantly improved SCO-induced memory impairment and restored synaptic protein expression (synaptophysin, synapsin1, and postsynaptic density protein 95) in the hippocampus. Additionally, PS enhanced brain-derived neurotrophic factor (BDNF) signaling and activated the extracellular signal-regulated kinase/CAMP response element binding protein (ERK-CREB) pathway, essential for synaptic plasticity. Our findings demonstrate that PS mitigates SCO-induced memory dysfunction by protecting synaptic integrity and activating the BDNF-ERK-CREB signaling pathway, indicating the potential of PS as a natural intervention for treating memory deficits.
참고문헌 (38)
- Hou Y, "Ageing as a risk factor for neurodegenerative disease", Nat. Rev. Neurol, 15, pp.565~581 (2019)
- Azam S, "The ageing brain : molecular and cellular basis of neurodegeneration", Front. Cell Dev. Biol, 9, pp.683459~ (2021)
- Delgado-Saborit JM, "A critical review of the epidemiological evidence of effects of air pollution on dementia, cognitive function and cognitive decline in adult population", Sci. Total Environ, 757, pp.143734~ (2021)
- Subramanian J, "Synaptic loss in Alzheimer's disease : mechanistic insights provided by two-photon in vivo imaging of transgenic mouse models", Front. Cell. Neurosci, 14, pp.592607~ (2020)
- Valcarcel-Ares MN, "Obesity in aging exacerbates neuroinflammation, dysregulating synaptic function-related genes and altering eicosanoid synthesis in the mouse hippocampus : potential role in impaired synaptic plasticity and cognitive decline", J. Gerontol. A, 74, pp.290~298 (2019)
- Kwon SE, "Synaptophysin regulates the kinetics of synaptic vesicle endocytosis in central neurons", Neuron, 70, pp.847~854 (2011)
- Ugalde-Triviño L, "PSD-95 : an effective target for stroke therapy using neuroprotective peptides", Int. J. Mol. Sci, 22, pp.12585~ (2021)
- Davis S, "Mitogen-activated protein kinase", extracellular regulated kinase signalling and memory stabilization : a review, 2006, pp.5, 61~72
- Kumar LR, "Phlorotannins–bioactivity and extraction perspectives", J. Appl. Phycol, 34, pp.2173~2185 (2022)
- Catarino MD, "Brown algae phlorotannins : a marine alternative to break the oxidative stress, inflammation and cancer network", Foods, 10, pp.1478~ (2021)
- Kwon YJ, "Therapeutic effects of phlorotannins in the treatment of neurodegenerative disorders", Front. Mol. Neurosci, 16, pp.1193590~ (2023)
- Nho JA, "Neuroprotective effects of phlorotannin-rich extract from brown seaweed Ecklonia cava on neuronal PC-12 and SH-SY5Y cells with oxidative stress", J. Microbiol. Biotechnol, 30, pp.359~ (2020)
- Yoon M, "Effects of chronic administration and withdrawal of phlorotannin supplement on sleep-wake profiles in mice : a comparative study with the hypnotic drug diazepam", J. Funct. Foods, 115, pp.106117~ (2024)
- Cho S, "Marine polyphenol phlorotannins promote non-rapid eye movement sleep in mice via the benzodiazepine site of the GABA A receptor", Psychopharmacology, 231, pp.2825~2837 (2014)
- Park SJ, "Amyrin attenuates scopolamine-induced cognitive impairment in mice", Biol. Pharm. Bull, 37, pp.1207~1213 (2014)
- Yadang FSA, "Scopolamine‐induced memory impairment in mice: neuroprotective effects of Carissa edulis (Forssk.) Valh (Apocynaceae) aqueous extract", Int. J. Alzheimer's Dis, 2020, pp.6372059~ (2020)
- Kwon S, "A standardized phlorotannin supplement attenuates caffeine-induced sleep disruption in mice", Nutrients, 11, pp.556~ (2019)
- Tucker LB, "Performance of male and female C57BL", 6J mice on motor and cognitive tasks commonly used in pre-clinical traumatic brain injury research, 2016, pp.33, 880~894
- Lueptow LM, "Novel object recognition test for the investigation of learning and memory in mice", J. Vis. Exp, 30, pp.e55718~ (2017)
- Um MY, "Phlorotannin-rich fraction from Ishige foliacea brown seaweed prevents the scopolamine-induced memory impairment via regulation of ERK-CREB-BDNF pathway", J. Funct. Foods, 40, pp.110~116 (2018)
- Morris R, "Developments of a water-maze procedure for studying spatial learning in the rat", J. Neurosci. Methods, 11, pp.47~60 (1984)
- Nosheny RL, "Variables associated with hippocampal atrophy rate in normal aging and mild cognitive impairment", Neurobiol. Aging, 36, pp.273~282 (2015)
- Mi Y, "EGCG ameliorates high-fat–and high-fructose-induced cognitive defects by regulating the IRS", AKT and ERK, BDNF signaling pathways in the CNS, pp.FASEB J, 2017[DOI]
- Lochner M, "The muscarinic antagonists scopolamine and atropine are competitive antagonists at 5-HT3receptors", Neuropharmacology, 108, pp.220~228 (2016)
- Kwon SH, "Loganin improves learning and memory impairments induced by scopolamine in mice", Eur. J. Pharmacol, 619, pp.44~49 (2009)
- Han HJ, "Mixture of phlorotannin and fucoidan from Ecklonia cava prevents the aβ-induced cognitive decline with mitochondrial and cholinergic activation", Mar. Drugs, 19, pp.434~ (2021)
- Park SK, "Ecklonia cava attenuates PM2. 5-induced cognitive decline through mitochondrial activation and anti-inflammatory effect", Mar. Drugs, 19, pp.131~ (2021)
- Myung CS, "Improvement of memory by dieckol and phlorofucofuroeckol in ethanol-treated mice : possible involvement of the inhibition of acetylcholinesterase", Arch. Pharm. Res, 28, pp.691~698 (2005)
- Yang EJ, "Phloroglucinol attenuates the cognitive deficits of the 5XFAD mouse model of Alzheimer’s disease", PLoS One, 10, pp.e0135686~ (2015)
- O'Reilly KC, "Synaptic plasticity", dysplasticity, process memory and item memory in rodent models of mental dysfunction, 2019, pp.207, 22~36
- Hilfiker S, "Synapsins as regulators of neurotransmitter release", Philos. Trans. R. Soc. B, Biol. Sci, 354, pp.269~279 (1999)
- Colucci-D’Amato L, "Neurotrophic factor BDNF, physiological functions and therapeutic potential in depression, neurodegeneration and brain cancer", Int. J. Mol. Sci, 21, pp.7777~ (2020)
- Rauti R, "BDNF impact on synaptic dynamics : extra or intracellular long-term release differently regulates cultured hippocampal synapses", Mol. Brain, 13, pp.43~ (2020)
- AlRuwaili R, "The possible role of brain-derived neurotrophic factor in epilepsy", Neurochem. Res, 49, pp.533~547 (2024)
- Lee SS, "Treadmill exercise ameliorates memory impairment through ERK-Akt-CREB-BDNF signaling pathway in cerebral ischemia gerbils", J. Exerc. Rehabil, 16, pp.49~57 (2020)
- Esvald EE, "CREB family transcription factors are major mediators of BDNF transcriptional autoregulation in cortical neurons", J. Neurosci, 40, pp.1405~1426 (2020)
- Alonso M, "ERK1", 2 activation is necessary for BDNF to increase dendritic spine density in hippocampal CA1 pyramidal neurons, 2004, pp.11, 172~178
- Lu Y, "BDNF : a key regulator for protein synthesis-dependent LTP and long-term memory?", Neurobiol. Learn. Mem, 89, pp.312~323 (2008)
