Ginkgo Biloba Extract Ameliorates Scopolamine-induced Memory Deficits via Rescuing Synaptic Damage

Gui-jiao Zhang , Dong Zheng , Huan Yu , Xiao-ping Luo , Wei Wu

Current Medical Science ›› 2022, Vol. 42 ›› Issue (3) : 474 -482.

PDF
Current Medical Science ›› 2022, Vol. 42 ›› Issue (3) : 474 -482. DOI: 10.1007/s11596-022-2582-8
Article

Ginkgo Biloba Extract Ameliorates Scopolamine-induced Memory Deficits via Rescuing Synaptic Damage

Author information +
History +
PDF

Abstract

Objective

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder. Emerging evidence suggests that synaptic dysfunction is associated with the onset and progression of AD. Interestingly, Ginkgo biloba extract (EGb) is one of the most frequently investigated herbal medicines for enhancing cognition and alleviating neurodegenerative dementia. This study aimed to investigate the effect and the mechanism of EGb on AD-like synaptic disorders.

Methods

Scopolamine (SCO)-induced rats were used to mimic AD-like memory deficits. Morris water maze test and fear conditioning test were conducted to evaluate the memory status of rats in response to different treatments. Then, the synapse alterations were assessed by Golgi staining, and Western blotting was conducted to assess the protein expression of PSD95, GluN2B, synapsin-1, and synaptophysin. Reverse transcription quantitative polymerase chain reaction was applied to detect the mRNA expression of PSD95 and the levels of miR-1-3p/miR-206-3p.

Results

EGb supplement alleviated the learning and memory deficits induced by SCO in behavioral experiments. Moreover, EGb treatment attenuated synaptic damage elicited by SCO, manifested as increased dendritic spine density and the proportion of mushroom-type spines in hippocampal neurons. Further investigation indicated that EGb rescued the expression of synaptic-related proteins, especially PSD95, and decreased the levels of miR-1-3p/miR-206-3p in the rat hippocampus.

Conclusion

The application of EGb effectively treats SCO-induced memory impairments probably by suppressing miR-1-3p/miR-206-3p and elevating the expression of PSD95.

Keywords

Ginkgo biloba extract / Alzheimer’s disease / synapse / PSD95 / MiR-1 / MiR-206

Cite this article

Download citation ▾
Gui-jiao Zhang, Dong Zheng, Huan Yu, Xiao-ping Luo, Wei Wu. Ginkgo Biloba Extract Ameliorates Scopolamine-induced Memory Deficits via Rescuing Synaptic Damage. Current Medical Science, 2022, 42(3): 474-482 DOI:10.1007/s11596-022-2582-8

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

ArendtT. Synaptic degeneration in Alzheimer’s disease. Acta Neuropathol, 2009, 118(1): 167-179

[2]

RajmohanR, ReddyPH. Amyloid-Beta and Phosphorylated Tau Accumulations Cause Abnormalities at Synapses of Alzheimer’s disease Neurons. J Alzheimers Dis, 2017, 57(4): 975-999

[3]

TchantchouF, XuY, WuY, et al.. EGb 761 enhances adult hippocampal neurogenesis and phosphorylation of CREB in transgenic mouse model of Alzheimer’s disease. Faseb J, 2007, 21(10): 2400-2408

[4]

TanakaK, GaldurózRF, GobbiLT, et al.. Ginkgo biloba extract in an animal model of Parkinson’s disease: a systematic review. Curr Neuropharmacol, 2013, 11(4): 430-435

[5]

HuangDS, LinHY, Lee-ChenGJ, et al.. Treatment with a Ginkgo biloba extract, EGb 761, inhibits excitotoxicity in an animal model of spinocerebellar ataxia type 17. Drug Des Devel Ther, 2016, 10: 723-731

[6]

ZhangWF, TanYL, ZhangXY, et al.. Extract of Ginkgo biloba treatment for tardive dyskinesia in schizophrenia: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry, 2011, 72(5): 615-621

[7]

ChopinP, BrileyM. Effects of four non-cholinergic cognitive enhancers in comparison with tacrine and galanthamine on scopolamine-induced amnesia in rats. Psychopharmacology (Berl), 1992, 106(1): 26-30

[8]

ZhangJ, WangJ, ZhouGS, et al.. Studies of the Anti-amnesic Effects and Mechanisms of Single and Combined Use of Donepezil and Ginkgo Ketoester Tablet on Scopolamine-Induced Memory Impairment in Mice. Oxid Med Cell Longev, 2019, 2019: 8636835

[9]

FelekkisK, TouvanaE, StefanouC, et al.. microRNAs: a newly described class of encoded molecules that play a role in health and disease. Hippokratia, 2010, 14(4): 236-240

[10]

YamashitaH, SurapureddiS, KoviRC, et al.. Unique microRNA alterations in hepatocellular carcinomas arising either spontaneously or due to chronic exposure to Ginkgo biloba extract (GBE) in B6C3F1/N mice. Arch Toxicol, 2020, 94(7): 2523-2541

[11]

YeY, XuH, SuX, et al.. Role of MicroRNA in Governing Synaptic Plasticity. Neural Plast, 2016, 2016: 4959523

[12]

ZengK, LiM, HuJ, et al.. Ginkgo biloba Extract EGb761 Attenuates Hyperhomocysteinemia-induced AD Like Tau Hyperphosphorylation and Cognitive Impairment in Rats. Curr Alzheimer Res, 2018, 15(1): 89-99

[13]

WangX, WangZH, WuYY, et al.. Melatonin attenuates scopolamine-induced memory/synaptic disorder by rescuing EPACs/miR-124/Egr1 pathway. Mol Neurobiol, 2013, 47(1): 373-381

[14]

ShojiH, TakaoK, HattoriS, et al.. Contextual and cued fear conditioning test using a video analyzing system in mice. J Vis Exp, 2014, 85: 50871

[15]

Tatem KS, Quinn JL, Phadke A, et al. Behavioral and locomotor measurements using an open field activity monitoring system for skeletal muscle diseases. J Vis Exp, 2014(91):51785

[16]

KhanalP, HotulainenP. Dendritic Spine Initiation in Brain Development, Learning and Diseases and Impact of BAR-Domain Proteins. Cells, 2021, 10(9): 2392

[17]

KumarS, ReddyPH. The role of synaptic microRNAs in Alzheimer’s disease. Biochim Biophys Acta Mol Basis Dis, 2020, 1866(12): 165937

[18]

McGearySE, LinKS, ShiCY, et al.. The biochemical basis of microRNA targeting efficacy. Science, 2019, 366(6472): eaav1741

[19]

KiriakidouM, NelsonPT, KouranovA, et al.. A combined computational-experimental approach predicts human microRNA targets. Genes Dev, 2004, 18(10): 1165-1178

[20]

WongN, WangX. miRDB: an online resource for microRNA target prediction and functional annotations. Nucleic Acids Res, 2015, 43(Databaseissue): D146-152

[21]

GuanZF, ZhangXM, TaoYH, et al.. EGb761 improves the cognitive function of elderly db/db(—/—) diabetic mice by regulating the beclin-1 and NF-κB signaling pathways. Metab Brain Dis, 2018, 33(6): 1887-1897

[22]

YaoZH, WangJ, YuanJP, et al.. EGB761 ameliorates chronic cerebral hypoperfusion-induced cognitive dysfunction and synaptic plasticity impairment. Aging (Albany NY), 2021, 13(7): 9522-9541

[23]

NathanP. Can the cognitive enhancing effects of ginkgo biloba be explained by its pharmacology?. Med Hypotheses, 2000, 55(6): 491-493

[24]

SinghSK, SrivastavS, CastellaniRJ, et al.. Neuroprotective and Antioxidant Effect of Ginkgo biloba Extract Against AD and Other Neurological Disorders. Neurotherapeutics, 2019, 16(3): 666-674

[25]

RenC, JiYQ, LiuH, et al.. Effects of Ginkgo biloba extract EGb761 on neural differentiation of stem cells offer new hope for neurological disease treatment. Neural Regen Res, 2019, 14(7): 1152-1157

[26]

LejriI, GrimmA, EckertA. Ginkgo biloba extract increases neurite outgrowth and activates the Akt/mTOR pathway. PLoS One, 2019, 14(12): e0225761

[27]

Siedlecki-WullichD, Miñano-MolinaAJ, Rodríguez-ÁlvarezJ. microRNAs as Early Biomarkers of Alzheimer’s Disease: A Synaptic Perspective. Cells, 2021, 10(1): 113

[28]

ZhengK, HuF, ZhouY, et al.. miR-135a-5p mediates memory and synaptic impairments via the Rock2/Adducin1 signaling pathway in a mouse model of Alzheimer’s disease. Nat Commun, 2021, 12(1): 1903

[29]

MaG, WangY, LiY, et al.. MiR-206, a key modulator of skeletal muscle development and disease. Int J Biol Sci, 2015, 11(3): 345-352

[30]

PiscopoP, LacorteE, FeligioniM, et al.. MicroRNAs and mild cognitive impairment: A systematic review. Ageing Res Rev, 2019, 50: 131-141

[31]

LeeST, ChuK, JungKH, et al.. miR-206 regulates brain-derived neurotrophic factor in Alzheimer disease model. Ann Neurol, 2012, 72(2): 269-277

[32]

EivaniM, AlijanpourS, ArefianE, et al.. Corticolimbic analysis of microRNAs and protein expressions in scopolamine-induced memory loss under stress. Neurobiol Learn Mem, 2019, 164: 107065

[33]

ColeyAA, GaoWJ. PSD95: A synaptic protein implicated in schizophrenia or autism?. Prog Neuropsychopharmacol Biol Psychiatry, 2018, 82: 187-194

[34]

HansenT, OlsenL, LindowM, et al.. Brain expressed microRNAs implicated in schizophrenia etiology. PLoS One, 2007, 2(9): e873

[35]

PrangeO, MurphyTH. Modular transport of postsynaptic density-95 clusters and association with stable spine precursors during early development of cortical neurons. J Neurosci, 2001, 21(23): 9325-9333

[36]

LiuJ, ChangL, RoselliF, et al.. Amyloid-β induces caspase-dependent loss of PSD-95 and synaptophysin through NMDA receptors. J Alzheimers Dis, 2010, 22(2): 541-556

[37]

RaiR, SinghHK, PrasadS. A Special Extract of Bacopa monnieri (CDRI-08) Restores Learning and Memory by Upregulating Expression of the NMDA Receptor Subunit GluN2B in the Brain of Scopolamine-Induced Amnesic Mice. Evid Based Complement Alternat Med, 2015, 2015: 254303

[38]

FalsafiSK, DeliA, HögerH, et al.. Scopolamine administration modulates muscarinic, nicotinic and NMDA receptor systems. PLoS One, 2012, 7(2): e32082

[39]

TerryAVJr.LevinED, BuccafuscoJJAnimal Models of Cognitive Impairment, 2006, Boca Raton (FL), CRC Press/Taylor & Francis

[40]

SvobodaJ, PopelikovaA, StuchlikA. Drugs Interfering with Muscarinic Acetylcholine Receptors and Their Effects on Place Navigation. Front Psychiatry, 2017, 8: 215

AI Summary AI Mindmap
PDF

77

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/