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http://dx.doi.org/10.1016/j.jgr.2017.03.010

Ginsenoside Rg1 modulates medial prefrontal cortical firing and suppresses the hippocampo-medial prefrontal cortical long-term potentiation  

Ghaeminia, Mehdy (Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System)
Rajkumar, Ramamoorthy (Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System)
Koh, Hwee-Ling (Department of Pharmacy, Faculty of Science, National University of Singapore)
Dawe, Gavin S. (Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System)
Tan, Chay Hoon (Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System)
Publication Information
Journal of Ginseng Research / v.42, no.3, 2018 , pp. 298-303 More about this Journal
Abstract
Background: Panax ginseng is one of the most commonly used medicinal herbs worldwide for a variety of therapeutic properties including neurocognitive effects. Ginsenoside Rg1 is one of the most abundant active chemical constituents of this herb with known neuroprotective, anxiolytic, and cognition improving effects. Methods: We investigated the effects of Rg1 on the medial prefrontal cortex (mPFC), a key brain region involved in cognition, information processing, working memory, and decision making. In this study, the effects of systemic administration of Rg1 (1 mg/kg, 3 mg/kg, or 10 mg/kg) on (1) spontaneous firing of the medial prefrontal cortical neurons and (2) long-term potentiation (LTP) in the hippocampal-medial prefrontal cortical (HP-mPFC) pathway were investigated in male Sprague-Dawley rats. Results: The spontaneous neuronal activity of approximately 50% the recorded pyramidal cells in the mPFC was suppressed by Rg1. In addition, Rg1 attenuated LTP in the HP-mPFC pathway. These effects were not dose-dependent. Conclusion: This report suggests that acute treatment of Rg1 impairs LTP in the HP-mPFC pathway, perhaps by suppressing the firing of a subset of mPFC neurons that may contribute to the neurocognitive effects of Rg1.
Keywords
ginsenoside Rg1; hippocampus; long-term potentiation; medical prefrontal cortex; single unit;
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1 Jia L, Zhao Y, Liang XJ. Current evaluation of the millennium phytomedicinedginseng (II): Collected chemical entities, modern pharmacology, and clinical applications emanated from traditional Chinese medicine. Curr Med Chem 2009;16:2924-42.   DOI
2 Kim HJ, Kim P, Shin CY. A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system. J Ginseng Res 2013;37:8-29.   DOI
3 Ong WY, Farooqui T, Koh HL, Farooqui AA, Ling EA. Protective effects of ginseng on neurological disorders. Front Aging Neurosci 2015;7:129.
4 Christensen LP. Ginsenosides chemistry, biosynthesis, analysis, and potential health effects. Adv Food Nutr Res 2009;55:1-99.
5 Mook-Jung I, Hong HS, Boo JH, Lee KH, Yun SH, Cheong MY, Joo I, Huh K, Jung MW. Ginsenoside Rb1 and Rg1 improve spatial learning and increase hippocampal synaptophysin level in mice. J Neurosci Res 2001;63:509-15.   DOI
6 Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 6th ed. Amsterdam: Academic Press/Elsevier; 2007.
7 Zhu J, Mu X, Zeng J, Xu C, Liu J, Zhang M, Li C, Chen J, Li T, Wang Y. Ginsenoside Rg1 prevents cognitive impairment and hippocampus senescence in a rat model of d-galactose-induced aging. PloS One 2014;9:e101291.   DOI
8 Wang XY, Zhang JT. NO mediates ginsenoside Rg1-induced long-term potentiation in anesthetized rats. Acta Pharmacol Sin 2001;22:1099-102.
9 Shi YQ, Huang TW, Chen LM, Pan XD, Zhang J, Zhu YG, Chen XC. Ginsenoside Rg1 attenuates amyloid-beta content, regulates PKA/CREB activity, and improves cognitive performance in SAMP8 mice. J Alzheimer's Dis 2010;19:977-89.   DOI
10 Fang F, Chen X, Huang T, Lue LF, Luddy JS, Yan SS. Multi-faced neuroprotective effects of Ginsenoside Rg1 in an Alzheimer mouse model. Biochim Biophys Acta 2012;1822:286-92.   DOI
11 Qi D, Zhu Y, Wen L, Liu Q, Qiao H. Ginsenoside Rg1 restores the impairment of learning induced by chronic morphine administration in rats. J Psychopharmacol 2009;23:74-83.   DOI
12 Kohn DF. Anesthesia and analgesia in laboratory animals. San Diego: Academic Press; 1997. xvii, 426 pp.
13 Zhu G, Wang Y, Li J, Wang J. Chronic treatment with ginsenoside Rg1 promotes memory and hippocampal long-term potentiation in middle-aged mice. Neuroscience 2015;292:81-9.   DOI
14 Abe K, Cho SI, Kitagawa I, Nishiyama N, Saito H. Differential effects of ginsenoside Rb1 and malonylginsenoside Rb1 on long-term potentiation in the dentate gyrus of rats. Brain Res 1994;649:7-11.   DOI
15 Xue W, Liu Y, Qi WY, Gao Y, Li M, Shi AX, Li KX. Pharmacokinetics of ginsenoside Rg1 in rat medial prefrontal cortex, hippocampus, and lateral ventricle after subcutaneous administration. J Asian Nat Prod Res 2016;18:587-95.   DOI
16 Flecknell P. Laboratory animal anaesthesia. London: Academic Press; 2009.
17 Bai W, Liu T, Yi H, Li S, Tian X. Anticipatory activity in rat medial prefrontal cortex during a working memory task. Neurosci Bull 2012;28:693-703.   DOI
18 Hyman JM, Zilli EA, Paley AM, Hasselmo ME. Working memory performance correlates with prefrontalehippocampal theta interactions but not with prefrontal neuron firing rates. Front Integr Neurosci 2010;4:2.
19 Wang Q, Sun LH, Jia W, Liu XM, Dang HX, Mai WL, Wang N, Steinmetz A, Wang YQ, Xu CJ. Comparison of ginsenosides Rg1 and Rb1 for their effects on improving scopolamine-induced learning and memory impairment in mice. Phytother Res 2010;24:1748-54.   DOI
20 Wang Y, Kan H, Yin Y, Wu W, Hu W, Wang M, Li W, Li W. Protective effects of ginsenoside Rg1 on chronic restraint stress induced learning and memory impairments in male mice. Pharmacol Biochem Behav 2014;120:73-81.   DOI
21 Wang YZ, Chen J, Chu SF, Wang YS, Wang XY, Chen NH, Zhang JT. Improvement of memory in mice and increase of hippocampal excitability in rats by ginsenoside Rg1's metabolites ginsenoside Rh1 and protopanaxatriol. J Pharmacol Sci 2009;109:504-10.   DOI
22 Wang XY, Chen J, Zhang JT. Effect of ginsenoside Rg1 on learning and memory impairment induced by beta-amyloid peptide(25-35) and its mechanism of action. Yao Xue Xue Bao [Acta Pharm Sin] 2001;36:1-4.
23 Chen ZY, Du TM, Chen SC. Effects of ginsenoside Rg1 on learning and memory function and morphology of hippocampal neurons of rats with electrical hippocampal injuries. Nan Fang Yi Ke Da Xue Xue Bao [J Southern Med Univ] 2011;31:1039-42.
24 Wu W, Yang JQ, He ZY. Effect of ginsenoside Rg1 on the spatial learningmemory ability in dementia rats after transplanted with bone marrow mesenchymal stem cells. Zhongguo Zhong Xi Yi Jie He Za Zhi [Chin J Integrated Tradit Western Medicine] 2011;31:799-802.
25 Zhang X, Wang J, Xing Y, Gong L, Li H, Wu Z, Li Y, Wang J, Wang Y, Dong L, et al. Effects of ginsenoside Rg1 or 17beta-estradiol on a cognitively impaired, ovariectomized rat model of Alzheimer's disease. Neuroscience 2012;220:191-200.   DOI
26 Groenewegen HJ, Wright CI, Uylings HB. The anatomical relationships of the prefrontal cortex with limbic structures and the basal ganglia. J Psychopharmacol 1997;11:99-106.   DOI
27 Jackson ME, Moghaddam B. Distinct patterns of plasticity in prefrontal cortex neurons that encode slow and fast responses to stress. Eur J Neurosci 2006;24:1702-10.   DOI
28 Gulley JM, Stanis JJ. Adaptations in medial prefrontal cortex function associated with amphetamine-induced behavioral sensitization. Neuroscience 2010;166:615-24.   DOI
29 Ruiz-Mejias M, Ciria-Suarez L, Mattia M, Sanchez-Vives MV. Slow and fast rhythms generated in the cerebral cortex of the anesthetized mouse. J Neurophysiol 2011;106:2910-21.   DOI
30 Zheng X, Liang Y, Kang A, Ma SJ, Xing L, Zhou YY, Dai C, Xie H, Xie L, Wang GJ, et al. Peripheral immunomodulation with ginsenoside Rg1 ameliorates neuroinflammation-induced behavioral deficits in rats. Neuroscience 2014;256:210-22.   DOI
31 Dalley JW, Cardinal RN, Robbins TW. Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates. Neurosci Biobehav Rev 2004;28:771-84.   DOI
32 Hoover WB, Vertes RP. Anatomical analysis of afferent projections to the medial prefrontal cortex in the rat. Brain Struct Funct 2007;212:149-79.   DOI
33 Lim EP, Tan CH, Jay TM, Dawe GS. Locus coeruleus stimulation and noradrenergic modulation of hippocampo-prefrontal cortex long-term potentiation. Int J Neuropsychopharmacol 2010;13:1219-31.   DOI
34 Rajkumar R, Wu Y, Farooq U, Tan WH, Dawe GS. Stress activates the nucleus incertus and modulates plasticity in the hippocampo-medial prefrontal cortical pathway. Brain Res Bull 2016;120:83-9.   DOI
35 Farooq U, Rajkumar R, Sukumaran S, Wu Y, Tan WH, Dawe GS. Corticotropinreleasing factor infusion into nucleus incertus suppresses medial prefrontal cortical activity and hippocampo-medial prefrontal cortical long-term potentiation. Eur J Neurosci 2013;38:2516-25.   DOI
36 Shi J, Xue W, Zhao WJ, Li KX. Pharmacokinetics and dopamine/acetylcholine releasing effects of ginsenoside Re in hippocampus and mPFC of freely moving rats. Acta Pharmacol Sin 2013;34:214-20.   DOI
37 Wang XY, Zhang JT. Effects of ginsenoside Rg1 on synaptic plasticity of freely moving rats and its mechanism of action. Acta Pharmacol Sin 2001;22:657-62.
38 Xu L, Wang XY, Liu SL, Zhang JT. Two forms of long-term potentiation induced by different compounds. J Asian Nat Prod Res 2007;9:217-22.   DOI
39 Zhao R, McDaniel WF. Ginseng improves strategic learning by normal and brain-damaged rats. Neuroreport 1998;9:1619-24.   DOI