nach oben

NeuroMolecular Medicine

Erschienen in:

01.06.2014 | Original Paper

Attenuation of Reserpine-Induced Pain/Depression Dyad by Gentiopicroside Through Downregulation of GluN2B Receptors in the Amygdala of Mice

verfasst von: Shui-bing Liu, Rong Zhao, Xu-sheng Li, Hong-ju Guo, Zhen Tian, Nan Zhang, Guo-dong Gao, Ming-gao Zhao

Erschienen in: NeuroMolecular Medicine | Ausgabe 2/2014

Einloggen, um Zugang zu erhalten

Abstract

Epidemiological studies demonstrate that pain frequently occurs comorbid with depression. Gentiopicroside (Gent) is a secoiridoid compound isolated from Gentiana lutea that exhibits analgesic properties and inhibits the expression of GluN2B-containing N-methyl-d-aspartate (NMDA) receptors in the anterior cingulate cortex of mice. However, the effects of Gent on the reserpine-induced pain/depression dyad and its underlying mechanisms are unclear. Reserpine administration (1 mg/kg subcutaneous daily for 3 days) caused a significant decrease in the nociceptive threshold as evidenced by the reduced paw withdrawal latency in response to a radiant heat source and mechanical allodynia. Behavioral detection indicated a significant increase in immobility time during a forced swim test, as well as decreased time in the central area and total travel distance in an open field test. Furthermore, reserpinized animals exhibited increased oxidative stress. Systemic Gent administration dose-dependently ameliorated the behavioral deficits associated with reserpine-induced pain/depression dyad. At the same time, the decrease in biogenic amine levels (norepinephrine, dopamine, and serotonin) was integrated with the increase in caspase-3 levels and GluN2B-containing NMDA receptors in the amygdala of the reserpine-injected mice. Gent significantly reversed the changes in the levels of biogenic amines, caspase-3, and GluN2B-containing NMDA receptors in amygdala. However, Gent did not affect the expression of GluN2A-containing NMDA receptors. The inhibitory effects of Gent on oxidative stress were occluded by simultaneous treatment of GluN2B receptors antagonist Ro25-6981. Our study provides strong evidence that Gent inhibits reserpine-induced pain/depression dyad by downregulating GluN2B receptors in the amygdala.

Amaral, O. B., & Roesler, R. (2008). Targeting the NMDA receptor for fear-related disorders. Recent Patents on CNS Drug Discovery, 3(3), 166–178.PubMedCrossRef

Arora, V., Kuhad, A., Tiwari, V., & Chopra, K. (2011). Curcumin ameliorates reserpine-induced pain-depression dyad: Behavioural, biochemical, neurochemical and molecular evidences. Psychoneuroendocrinology, 36(10), 1570–1581.PubMedCrossRef

Bair, M. J., Robinson, R. L., Katon, W., & Kroenke, K. (2003). Depression and pain comorbidity: A literature review. Archives of Internal Medicine, 163(20), 2433–2445.PubMedCrossRef

Bar, K. J., Wagner, G., Koschke, M., Boettger, S., Boettger, M. K., Schlosser, R., et al. (2007). Increased prefrontal activation during pain perception in major depression. Biological Psychiatry, 62(11), 1281–1287.PubMedCrossRef

Blackburn-Munro, G., & Blackburn-Munro, R. E. (2001). Chronic pain, chronic stress and depression: Coincidence or consequence? Journal of Neuroendocrinology, 13(12), 1009–1023.PubMedCrossRef

Blier, P., & Abbott, F. V. (2001). Putative mechanisms of action of antidepressant drugs in affective and anxiety disorders and pain. Journal of Psychiatry and Neuroscience, 26(1), 37–43.PubMedCentralPubMed

Cates, L. N., Roberts, A. J., Huitron-Resendiz, S., & Hedlund, P. B. (2013). Effects of lurasidone in behavioral models of depression. Role of the 5-HT receptor subtype. Neuropharmacology, 70C, 211–217.CrossRef

Chaplan, S. R., Bach, F. W., Pogrel, J. W., Chung, J. M., & Yaksh, T. L. (1994). Quantitative assessment of tactile allodynia in the rat paw. Journal of Neuroscience Methods, 53(1), 55–63.PubMedCrossRef

Chen, L., Liu, J. C., Zhang, X. N., Guo, Y. Y., Xu, Z. H., Cao, W., et al. (2008). Down-regulation of NR2B receptors partially contributes to analgesic effects of gentiopicroside in persistent inflammatory pain. Neuropharmacology, 54(8), 1175–1181.PubMedCrossRef

Ehrlich, I., Humeau, Y., Grenier, F., Ciocchi, S., Herry, C., & Luthi, A. (2009). Amygdala inhibitory circuits and the control of fear memory. Neuron, 62(6), 757–771.PubMedCrossRef

Elhwuegi, A. S. (2004). Central monoamines and their role in major depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 28(3), 435–451.PubMedCrossRef

Feng, B., Liu, J. C., Zhang, J., Ozaki, K., Guo, Y. Y., Yi, D. H., et al. (2013). Anxiolytic actions of motilin in the basolateral amygdala. Molecular Neurobiology, 47(3), 892–902.PubMedCrossRef

Guo, Y. Y., Liu, S. B., Cui, G. B., Ma, L., Feng, B., Xing, J. H., et al. (2012). Acute stress induces down-regulation of large-conductance Ca2+ -activated potassium channels in the lateral amygdala. Journal of Physiology, 590(Pt 4), 875–886.PubMedCentralPubMed

Hamilton, J. P., Siemer, M., & Gotlib, I. H. (2008). Amygdala volume in major depressive disorder: A meta-analysis of magnetic resonance imaging studies. Molecular Psychiatry, 13(11), 993–1000.PubMedCentralPubMedCrossRef

Hase, K., Li, J., Basnet, P., Xiong, Q., Takamura, S., Namba, T., et al. (1997). Hepatoprotective principles of Swertia japonica Makino on D-galactosamine/lipopolysaccharide-induced liver injury in mice. Chemical and Pharmaceutical Bulletin (Tokyo), 45(11), 1823–1827.CrossRef

Heydarpour, P., Salehi-Sadaghiani, M., Javadi-Paydar, M., Rahimian, R., Fakhfouri, G., Khosravi, M., et al. (2013). Estradiol reduces depressive-like behavior through inhibiting nitric oxide/cyclic GMP pathway in ovariectomized mice. Hormones and Behavior, 63(2), 361–369.PubMedCrossRef

Hu, J., Wang, Z., Guo, Y. Y., Zhang, X. N., Xu, Z. H., Liu, S. B., et al. (2009). A role of periaqueductal grey NR2B-containing NMDA receptor in mediating persistent inflammatory pain. Mol Pain, 5, 71.PubMedCentralPubMedCrossRef

Karolewicz, B., Szebeni, K., Gilmore, T., Maciag, D., Stockmeier, C. A., & Ordway, G. A. (2009). Elevated levels of NR2A and PSD-95 in the lateral amygdala in depression. International Journal of Neuropsychopharmacology, 12(2), 143–153.PubMedCentralPubMedCrossRef

Lakhan, S. E., Caro, M., & Hadzimichalis, N. (2013). NMDA receptor activity in neuropsychiatric disorders. Front Psychiatry, 4, 52.PubMedCentralPubMedCrossRef

Li, N., Lee, B., Liu, R. J., Banasr, M., Dwyer, J. M., Iwata, M., et al. (2010). mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science, 329(5994), 959–964.PubMedCentralPubMedCrossRef

Liu, S. B., Ma, L., Guo, H. J., Feng, B., Guo, Y. Y., Li, X. Q., et al. (2012a). Gentiopicroside attenuates morphine rewarding effect through downregulation of GluN2B receptors in nucleus accumbens. CNS Neuroscience & Therapeutics, 18(8), 652–658.CrossRef

Liu, Y., Wong, T. P., Aarts, M., Rooyakkers, A., Liu, L., Lai, T. W., et al. (2007). NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo. Journal of Neuroscience, 27(11), 2846–2857.PubMedCrossRef

Liu, L., Wong, T. P., Pozza, M. F., Lingenhoehl, K., Wang, Y., Sheng, M., et al. (2004). Role of NMDA receptor subtypes in governing the direction of hippocampal synaptic plasticity. Science, 304(5673), 1021–1024.PubMedCrossRef

Liu, S. B., Zhang, N., Guo, Y. Y., Zhao, R., Shi, T. Y., Feng, S. F., et al. (2012b). G-protein-coupled receptor 30 mediates rapid neuroprotective effects of estrogen via depression of NR2B-containing NMDA receptors. Journal of Neuroscience, 32(14), 4887–4900.PubMedCrossRef

Lohr, J. B., Kuczenski, R., & Niculescu, A. B. (2003). Oxidative mechanisms and tardive dyskinesia. CNS Drugs, 17(1), 47–62.PubMedCrossRef

Marks, D. M., Shah, M. J., Patkar, A. A., Masand, P. S., Park, G. Y., & Pae, C. U. (2009). Serotonin-norepinephrine reuptake inhibitors for pain control: Premise and promise. Current Neuropharmacology, 7(4), 331–336.PubMedCentralPubMedCrossRef

Molosh, A. I., Sajdyk, T. J., Truitt, W. A., Zhu, W., Oxford, G. S., & Shekhar, A. (2013). NPY Y(1) Receptors differentially modulate GABA(A) and NMDA receptors via divergent signal-transduction pathways to reduce excitability of amygdala neurons. Neuropsychopharmacology, 38, 1352.PubMedCrossRef

Monyer, H., Burnashev, N., Laurie, D. J., Sakmann, B., & Seeburg, P. H. (1994). Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron, 12(3), 529–540.PubMedCrossRef

Nash, J. E., Hill, M. P., & Brotchie, J. M. (1999). Antiparkinsonian actions of blockade of NR2B-containing NMDA receptors in the reserpine-treated rat. Experimental Neurology, 155(1), 42–48.PubMedCrossRef

Ozturk, N., Baser, K. H., Aydin, S., Ozturk, Y., & Calis, I. (2002). Effects of Gentiana lutea ssp. symphyandra on the central nervous system in mice. Phytotherapy Research, 16(7), 627–631.PubMedCrossRef

Ozturk, N., Korkmaz, S., Ozturk, Y., & Baser, K. H. (2006). Effects of gentiopicroside, sweroside and swertiamarine, secoiridoids from gentian (Gentiana lutea ssp. symphyandra), on cultured chicken embryonic fibroblasts. Planta Medica, 72(4), 289–294.PubMedCrossRef

Paoletti, P. (2011). Molecular basis of NMDA receptor functional diversity. European Journal of Neuroscience, 33(8), 1351–1365.PubMedCrossRef

Paoletti, P., Bellone, C., & Zhou, Q. (2013). NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease. Nature Reviews Neuroscience, 14(6), 383–400.PubMedCrossRef

Potvin, S., Grignon, S., & Marchand, S. (2009). Human evidence of a supra-spinal modulating role of dopamine on pain perception. Synapse (New York, N. Y.), 63(5), 390–402.CrossRef

Rainnie, D. G., Bergeron, R., Sajdyk, T. J., Patil, M., Gehlert, D. R., & Shekhar, A. (2004). Corticotrophin releasing factor-induced synaptic plasticity in the amygdala translates stress into emotional disorders. Journal of Neuroscience, 24(14), 3471–3479.PubMedCrossRef

Romano, J. M., & Turner, J. A. (1985). Chronic pain and depression: does the evidence support a relationship? Psychological Bulletin, 97(1), 18–34.PubMedCrossRef

Rouwette, T., Vanelderen, P., Roubos, E. W., Kozicz, T., & Vissers, K. (2012). The amygdala, a relay station for switching on and off pain. European Journal of Pain, 16(6), 782–792.PubMedCrossRef

Russell, I. J., Vaeroy, H., Javors, M., & Nyberg, F. (1992). Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis. Arthritis and Rheumatism, 35(5), 550–556.PubMedCrossRef

Sacher, J., Neumann, J., Funfstuck, T., Soliman, A., Villringer, A., & Schroeter, M. L. (2012). Mapping the depressed brain: A meta-analysis of structural and functional alterations in major depressive disorder. Journal of Affective Disorders, 140(2), 142–148.PubMedCrossRef

Senol, F. S., Tuzun, C. Y., Toker, G., & Orhan, I. E. (2012). An in vitro perspective to cholinesterase inhibitory and antioxidant activity of five Gentiana species and Gentianella caucasea. International Journal of Food Sciences and Nutrition, 63(7), 802–812.PubMedCrossRef

Smith, G. R. (1992). The epidemiology and treatment of depression when it coexists with somatoform disorders, somatization, or pain. General Hospital Psychiatry, 14(4), 265–272.PubMedCrossRef

Stanika, R. I., Pivovarova, N. B., Brantner, C. A., Watts, C. A., Winters, C. A., & Andrews, S. B. (2009). Coupling diverse routes of calcium entry to mitochondrial dysfunction and glutamate excitotoxicity. Proceedings of the National Academy of Sciences, 106, 9854–9859.CrossRef

Tasan, R. O., Nguyen, N. K., Weger, S., Sartori, S. B., Singewald, N., Heilbronn, R., et al. (2010). The central and basolateral amygdala are critical sites of neuropeptide Y/Y2 receptor-mediated regulation of anxiety and depression. Journal of Neuroscience, 30(18), 6282–6290.PubMedCentralPubMedCrossRef

Tye, K. M., Prakash, R., Kim, S. Y., Fenno, L. E., Grosenick, L., Zarabi, H., et al. (2011). Amygdala circuitry mediating reversible and bidirectional control of anxiety. Nature, 471(7338), 358–362.PubMedCentralPubMedCrossRef

Wang, S. H., de Oliveira Alvares, L., & Nader, K. (2009). Cellular and systems mechanisms of memory strength as a constraint on auditory fear reconsolidation. Nature Neuroscience, 12(7), 905–912.PubMedCrossRef

Wang, D., Yuan, X., Liu, T., Liu, L., Hu, Y., Wang, Z., et al. (2012). Neuroprotective activity of lavender oil on transient focal cerebral ischemia in mice. Molecules, 17(8), 9803–9817.PubMedCrossRef

Wu, L. J., Toyoda, H., Zhao, M. G., Lee, Y. S., Tang, J., Ko, S. W., et al. (2005). Upregulation of forebrain NMDA NR2B receptors contributes to behavioral sensitization after inflammation. Journal of Neuroscience, 25(48), 11107–11116.PubMedCrossRef

Wu, L. J., & Zhuo, M. (2009). Targeting the NMDA receptor subunit NR2B for the treatment of neuropathic pain. Neurotherapeutics, 6(4), 693–702.PubMedCrossRef

Wyllie, D. J., Livesey, M. R., & Hardingham, G. E. (2013). Influence of GluN2 subunit identity on NMDA receptor function. Neuropharmacology, 74, 4–17.PubMedCentralPubMedCrossRef

Xu, Y., Zhang, L., Shao, T., Ruan, L., Wang, L., Sun, J., et al. (2013). Ferulic acid increases pain threshold and ameliorates depression-like behaviors in reserpine-treated mice: Behavioral and neurobiological analyses. Metabolic Brain Disease, 28(4), 571–583.

Zarate, C. A, Jr, Singh, J. B., Carlson, P. J., Brutsche, N. E., Ameli, R., Luckenbaugh, D. A., et al. (2006). A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Archives of General Psychiatry, 63(8), 856–864.PubMedCrossRef

Zhao, M. G., Toyoda, H., Lee, Y. S., Wu, L. J., Ko, S. W., Zhang, X. H., et al. (2005). Roles of NMDA NR2B subtype receptor in prefrontal long-term potentiation and contextual fear memory. Neuron, 47(6), 859–872.PubMedCrossRef

Titel: Attenuation of Reserpine-Induced Pain/Depression Dyad by Gentiopicroside Through Downregulation of GluN2B Receptors in the Amygdala of Mice
verfasst von: Shui-bing Liu
Rong Zhao
Xu-sheng Li
Hong-ju Guo
Zhen Tian
Nan Zhang
Guo-dong Gao
Ming-gao Zhao
Publikationsdatum: 01.06.2014
Verlag: Springer US
Erschienen in: NeuroMolecular Medicine / Ausgabe 2/2014
Print ISSN: 1535-1084
Elektronische ISSN: 1559-1174
DOI: https://doi.org/10.1007/s12017-013-8280-8

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Wartezeit nicht kürzer, aber Arbeit flexibler

Psychotherapie Medizin aktuell

Fünf Jahren nach der Neugestaltung der Psychotherapie-Richtlinie wurden jetzt die Effekte der vorgenommenen Änderungen ausgewertet. Das Hauptziel der Novellierung war eine kürzere Wartezeit auf Therapieplätze. Dieses Ziel wurde nicht erreicht, es gab jedoch positive Auswirkungen auf andere Bereiche.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Attenuation of Reserpine-Induced Pain/Depression Dyad by Gentiopicroside Through Downregulation of GluN2B Receptors in the Amygdala of Mice

Abstract

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Wartezeit nicht kürzer, aber Arbeit flexibler

„Restriktion auf vier Wochen Therapie bei Schlaflosigkeit ist absurd!“

Stuhltransfusion könnte Fortschreiten von Parkinson-Symptomen bremsen

Frühe Tranexamsäure-Therapie nützt wenig bei Hirnblutungen

Update Neurologie

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2014

Correction of the Middle Eastern M712T Mutation Causing GNE Myopathy by Trans-Splicing

MiR-21 is an Ngf-Modulated MicroRNA That Supports Ngf Signaling and Regulates Neuronal Degeneration in PC12 Cells

ADHD Diagnosis May Influence the Association between Polymorphisms in Nicotinic Acetylcholine Receptor Genes and Tobacco Smoking

Deciphering the Roles of Trehalose and Hsp104 in the Inhibition of Aggregation of Mutant Huntingtin in a Yeast Model of Huntington’s Disease

Blockade of Nav1.8 Currents in Nociceptive Trigeminal Neurons Contributes to Anti-trigeminovascular Nociceptive Effect of Amitriptyline

Tellurium Compound AS101 Ameliorates Experimental Autoimmune Encephalomyelitis by VLA-4 Inhibition and Suppression of Monocyte and T Cell Infiltration into the CNS

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Wartezeit nicht kürzer, aber Arbeit flexibler

„Restriktion auf vier Wochen Therapie bei Schlaflosigkeit ist absurd!“

Stuhltransfusion könnte Fortschreiten von Parkinson-Symptomen bremsen

Frühe Tranexamsäure-Therapie nützt wenig bei Hirnblutungen

Update Neurologie