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Attenuation of 1-(m-Chlorophenyl)-Biguanide Induced Hippocampus-Dependent Memory Impairment by a Standardised Extract of Bacopa monniera (BESEB CDRI-08)

Abstract

Bacopa monniera is a well-known medhya-rasayana (memory enhancing and rejuvenating) plant in Indian traditional medical system of Ayurveda. The effect of a standardized extract of Bacopa monniera (BESEB CDRI-08) on serotonergic receptors and its influence on other neurotransmitters during hippocampal-dependent learning was evaluated in the present study. Wistar rat pups received a single dose of BESEB CDRI-08 during postnatal days 15–29 showed higher latency during hippocampal-dependent learning accompanied with enhanced 5HT3A receptor expression, serotonin and acetylcholine levels in hippocampus. Furthermore, 5HT3A receptor agonist 1-(m-chlorophenyl)-biguanide (mCPBG) impaired learning in the passive avoidance task followed by reduction of 5HT3A receptor expression, 5HT and ACh levels. Administration of BESEB CDRI-08 along with mCPBG attenuated mCPBG induced behavioral, molecular and neurochemical alterations. Our results suggest that BESEB CDRI-08 possibly acts on serotonergic system, which in turn influences the cholinergic system through 5-HT3 receptor to improve the hippocampal-dependent task.

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References

  1. Russo A, Borrelli F (2005) Bacopa monniera, a reputed nootropic plant: an overview. Phytomedicine 12:305–317

    PubMed  Article  CAS  Google Scholar 

  2. Singh HK, Dhawan BN (1982) Effect of Bacopa monniera Linn. (Brahmi) extract on avoidance responses in rats. J Ethnopharmacol 5:205–214

    PubMed  Article  CAS  Google Scholar 

  3. Singh HK, Dhawan BN (1997) Neuropsychopharmacological effects of the ayurvedic nootropic Bacopa monniera Linn. (Brahmi). Indian J Pharmacol 29:359–365

    Google Scholar 

  4. Das A, Shanker G, Nath C et al (2002) A comparative study in rodents of standardized extracts of Bacopa monniera and Ginkgo biloba: anticholinesterase and cognitive enhancing activities. Pharmacol Biochem Behav 73:893–900

    PubMed  Article  CAS  Google Scholar 

  5. Uabundit N, Wattanathorn J, Mucimapura S et al (2010) Cognitive enhancement and neuroprotective effects of Bacopa monnieri in Alzheimer’s disease model. J Ethnopharmacol 127:26–31

    PubMed  Article  Google Scholar 

  6. Vollala VR, Upadhya S, Nayak S (2010) Effect of Bacopa monniera Linn. (Brahmi) extract on learning and memory in rats: a behavioral study. J Vet Behav 5:69–74

    Article  Google Scholar 

  7. Singh HK, Rastogi RP, Srimal RC et al (1988) Effects of Bacosides A and B on avoidance response in rats. Phytother Res 2:70–75

    Article  CAS  Google Scholar 

  8. Vohora D, Pal SN, Pillai KK (2000) Protection from phenytoin-induced cognitive deficit by Bacopa monniera, a reputed Indian nootropic plant. J Ethnopharmacol 71:383–390

    PubMed  Article  CAS  Google Scholar 

  9. Khan R, Krishnakumar A, Paulose CS (2008) Decreased glutamate receptor binding and NMDA R1 gene expression in hippocampus of pilocarpine-induced epileptic rats: neuroprotective role of Bacopa monnieri extract. Epilepsy Behav 12:54–60

    PubMed  Article  Google Scholar 

  10. Mathew J, Gangadharan G, Kuruvilla KP et al (2011) Behavioral deficit and decreased GABA receptor functional regulation in the hippocampus of epileptic rats: effect of Bacopa monnieri. Neurochem Res 36:7–16

    Google Scholar 

  11. Hota SK, Barhwal K, Baitharu I et al (2009) Bacopa monniera leaf extract ameliorates hypobaric hypoxia induced spatial memory impairment. Neurobiol Dis 34:23–39

    PubMed  Article  CAS  Google Scholar 

  12. Prabhakar S, Saraf MK, Pandhi P et al (2008) Bacopa monniera exerts antiamnesic effect on diazepam-induced anterograde amnesia in mice. Psychopharmacol (Berl) 200:27–37

    Article  CAS  Google Scholar 

  13. Zhou Y, Peng L, Zhang WD et al (2009) Effect of triterpenoid saponins from Bacopa monniera on scopolamine-induced memory impairment in mice. Planta Med 75:568–574

    PubMed  Article  CAS  Google Scholar 

  14. Saraf MK, Prabhakar S, Khanduja KL et al (2011) Bacopa monniera attenuates scopolamine-induced impairment of spatial memory in mice. eCAM doi:10.1093/eCAM/neq038

  15. Saraf MK, Anand A, Prabhakar S (2010) Scopolamine induced amnesia is reversed by Bacopa monniera through participation of kinase-CREB pathway. Neurochem Res 35:279–287

    PubMed  Article  CAS  Google Scholar 

  16. Anand A, Saraf MK, Prabhakar S (2010) Antiamnesic effect of B. monniera on L-NNA induced amnesia involves calmodulin. Neurochem Res 35:1172–1181

    PubMed  Article  CAS  Google Scholar 

  17. Byrne JH, Kandel ER (1996) Presynaptic facilitation revisited: state and time dependence. J Neurosci 16:425–435

    PubMed  CAS  Google Scholar 

  18. Angers A, Storozhuk MV, Duchaine T et al (1998) Cloning and functional expression of an Aplysia 5-HT receptor negatively coupled to adenylate cyclase. J Neurosci 18:5586–5593

    PubMed  CAS  Google Scholar 

  19. Crow T, Xue-Bian JJ, Siddiqi V et al (2001) Serotonin activation of the ERK pathway in Hermissenda: contribution of calcium-dependent protein kinase C. J Neurochem 78:358–364

    PubMed  Article  CAS  Google Scholar 

  20. Cohen JE, Onyike CU, McElroy VL et al (2003) Pharmacological characterization of an adenylyl cyclase serotonin receptor in Aplysia: comparison with mammalian 5-HT receptors. J Neurophysiol 89:1440–1455

    PubMed  Article  CAS  Google Scholar 

  21. Meneses A (2003) A pharmacological analysis of an associative learning task: 5-HT1 to 5-HT7 receptor subtypes function on a Pavlovian/instrumental autoshaped memory. Learn Mem 10:363–372

    PubMed  Article  Google Scholar 

  22. Meneses A (1999) 5-HT system and cognition. Neurosci Biobehav Rev 23:1111–1125

    PubMed  Article  CAS  Google Scholar 

  23. Hoyer D, Clarke DE, Fozard JR et al (1994) International union of pharmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol Rev 46:157–203

    PubMed  CAS  Google Scholar 

  24. Hoyer D, Hannon JP, Martin GR (2002) Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav 71:533–554

    PubMed  Article  CAS  Google Scholar 

  25. MacDermott AB, Role LW, Siegelbaum SA (1999) Presynaptic ionotropic receptors and the control of transmitter release. Annu Rev Neurosci 22:443–485

    PubMed  Article  CAS  Google Scholar 

  26. Khakh BS, Henderson G (2000) Modulation of fast synaptic transmission by presynaptic ligand-gated cation channels. J Auton Nerv Syst 81:110–121

    PubMed  Article  CAS  Google Scholar 

  27. Van Hooft JA, Vijverberg HP (2000) 5-HT3 receptors and neurotransmitter release in the CNS: a nerve ending story? Trends Neurosci 23:605–610

    PubMed  Article  Google Scholar 

  28. Matsumoto M, Yoshioka M, Togashi H et al (1995) Modulation of norepinephrine release by serotonergic receptors in the rat hippocampus as measured by in vivo microdialysis. J Pharmacol Exp Ther 272:1044–1051

    PubMed  CAS  Google Scholar 

  29. McMahon LL, Kauer JA (1997) Hippocampal interneurons are excited via serotonin-gated ion channels. J Neurophys 78:2493–2502

    CAS  Google Scholar 

  30. Giovannini MG, Ceccarelli I, Molinari B et al (1998) Serotonergic modulation of acetylcholine release from cortex of freely moving rats. J Pharmacol Exp Ther 285:1219–1225

    PubMed  CAS  Google Scholar 

  31. Allan AM, Galindo R, Chynoweth J et al (2001) Conditioned place preference for cocaine is attenuated in mice overexpressing the 5-HT3 receptor. Psychopharmacology 158:18–27

    PubMed  Article  CAS  Google Scholar 

  32. Morales M, Battenberg E, de Lecea L et al (1996) The type 3 serotonin receptor is expressed in a subpopulation of GABAergic neurons in the rat neocortex and hippocampus. Brain Res 731:199–202

    PubMed  Article  CAS  Google Scholar 

  33. Harrell AV, Allan AM (2003) Improvements in hippocampal-dependent learning and detrimental attention in 5-HT3 receptor over expressing mice. Learn Mem 10:410–419

    PubMed  Article  Google Scholar 

  34. D’Agata V, Cavallaro S (2003) Hippocampal gene expression profiles in passive avoidance conditioning. Eur J Neurosci 18:2835–2841

    PubMed  Article  Google Scholar 

  35. Cavallaro S (2008) Genomic analysis of serotonin receptors in learning and memory. Behav Brain Res 195:2–6

    PubMed  Article  CAS  Google Scholar 

  36. Kilpatrick GJ, Butler A, Burridge J et al (1990) 1-(m-Chlorophenyl)-biguanide, a potent high affinity 5-HT3 receptor agonist. Eur J Pharmacol 182:193–197

    PubMed  Article  CAS  Google Scholar 

  37. Hong E, Meneses A (1996) Systemic injection of p-chloroamphetamine eliminates the effect of the 5-HT, compounds on learning. Pharmacol Biochem Behav 53:765–769

    PubMed  Article  CAS  Google Scholar 

  38. Meneses A (2007) Stimulation of 5-HT1A, 5-HT1B, 5-HT2A/2C, 5-HT3 and 5-HT4 receptors or 5-HT uptake inhibition: short- and long-term memory. Behav Brain Res 184:81–90

    PubMed  Article  CAS  Google Scholar 

  39. Marinissen MJ, Gutkind JS (2001) G-protein-coupled receptors and signaling networks: emerging paradigms. Trends Pharmacol Sci 22:368–376

    PubMed  Article  CAS  Google Scholar 

  40. Kroeze WK, Kristiansen K, Roth BL (2002) Molecular biology of serotonin receptors structure and function at the molecular level. Curr Top Med Chem 2:507–528

    PubMed  Article  CAS  Google Scholar 

  41. Kandel ER (2001) The molecular biology of memory storage: a dialogue between genes and synapse. Biosci Rep 21:565–611

    PubMed  Article  CAS  Google Scholar 

  42. Korzus E (2003) The relation of transcription to memory formation. Acta Biochim Pol 50:775–782

    PubMed  CAS  Google Scholar 

  43. Prisila Dulcy C, Ganesh A, Geraldine P, Akbarsha MA, Emmanuvel Rajan K (2010) Bacopa monniera leaf extract up-regulates tryptophan hydroxylase (TPH2) and serotonin transporter (SERT) expression: implications in memory formation. J Ethnopharmacol 134:55–61

    Google Scholar 

  44. Dobbing J, Sands J (1979) Comparative aspects of the brain growth spurt. Early Hum Dev 3:79–83

    PubMed  Article  CAS  Google Scholar 

  45. Bures J, Buresova O, Huston JP (1983) Techniques and basic experiments for study of brain and behaviour. Elsevier, Amsterdam, pp 148–160

    Google Scholar 

  46. Stubley-Weatherly L, Harding JW, Wright JW (1996) Effects of discrete kainic acid-induced hippocampal lesions on spatial and contextual learning and memory in rats. Brain Res 716:29–38

    PubMed  Article  CAS  Google Scholar 

  47. Misane I, Ögren SO (2000) Multiple 5-HT receptors in passive avoidance: comparative studies of p-chloroamphetamine and 8-OH-DPAT. Neuropsychopharmacology 22:168–190

    PubMed  Article  CAS  Google Scholar 

  48. Glowinski J, Iversen LL (1966) Regional studies of catecholamines in the rat brain. I. The disposition of [3H]norepinephrine, [3H]dopamine and [3H]dopa in various regions of the brain. J Neurochem 13:655–669

    PubMed  Article  CAS  Google Scholar 

  49. Chamizo C, Rubio JM, Moreno J et al (2001) Semi-quantitative analysis of multiple cytokines in canine peripheral blood mononuclear cells by a single tube RT–PCR. Vet Immunol Immunopathol 83:191–202

    PubMed  Article  CAS  Google Scholar 

  50. McCaffrey TA, Fu C, Du B et al (2000) High-level expression of Egr-1 and Egr-1- inducible genes in mouse and human atherosclerosis. J Clin Invest 105:653–662

    PubMed  Article  CAS  Google Scholar 

  51. Fink KB, Göthert M (2007) 5-HT receptor regulation of neurotransmitter release. Pharmacol Rev 59:360–417

    PubMed  CAS  Google Scholar 

  52. Turner TJ, Mokler DJ, Luebke JI (2004) Calcium influx through presynaptic 5-HT3 receptors facilitates GABA release in the hippocampus, in vitro slice and synaptosome studies. Neuroscience 129:703–718

    PubMed  Article  CAS  Google Scholar 

  53. Consolo S, Bertorelli R, Russi G et al (1994) Serotonergic facilitation of acetylcholine release in vivo from rat dorsal hippocampus via serotonin 5-HT3 receptors. J Neurochem 62:2254–2261

    PubMed  Article  CAS  Google Scholar 

  54. Siddiqui MF, Levey AI (1999) Cholinergic therapies in Alzhemer’s disease. Drugs Future 24:417–444

    Article  CAS  Google Scholar 

  55. Joshi H, Parle M (2006) Brahmi rasayana improves learning and memory in mice. Evid Based Complement Alternat Med 3:79–85

    PubMed  Article  Google Scholar 

  56. Dorostkar MM, Boehm S (2007) Opposite effects of presynaptic 5-HT3 receptor activation on spontaneous and action potential-evoked GABA release at hippocampal synapses. J Neurochem 100:395–405

    PubMed  Article  CAS  Google Scholar 

  57. Ramirez MJ, Cenarruzabeitia E, Lasheras B et al (1996) Involvement of GABA systems in acetylcholine release induced by 5HT3 receptor blockade in slices from rat entorhinal cortex. Brain Res 712:274–280

    PubMed  Article  CAS  Google Scholar 

  58. Díez-Ariza M, Ramírez MJ, Lasheras B et al (1998) Differential interaction between 5-HT3 receptors and GABAergic neurons inhibiting acetylcholine release in rat entorhinal cortex slices. Brain Res 801:228–232

    PubMed  Article  Google Scholar 

  59. Blandina P, Goldfarb J, Craddock-Royal B et al (1989) Release of endogenous dopamine by stimulation of 5-hydroxytryptamine3 receptors in rat striatum. J Pharmacol Exp Ther 251:803–809

    PubMed  CAS  Google Scholar 

  60. Alex KD, Pehek EA (2007) Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission. Pharmacol Ther 113:296–320

    PubMed  Article  CAS  Google Scholar 

  61. Campbell AD, Womer DE, Simon JR (1995) The 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide interacts with the dopamine transporter in rat brain synaptosomes. Eur J Pharmacol 290:157–162

    PubMed  Article  CAS  Google Scholar 

  62. Pardridge WM (1999) Blood-brain brarrier biology and methodology. J Neurovirol 5:556–569

    PubMed  Article  CAS  Google Scholar 

  63. Decker MW, McGaugh JL (1991) The role of interactions between the cholinergic system and other neuromodulatory systems in learning and memory. Synapse 7:151–168

    PubMed  Article  CAS  Google Scholar 

  64. Matsukawa M, Ogawa M, Nakadate K et al (1997) Serotonin and acetylcholine are crucial to maintain hippocampal synapses and memory acquisition in rats. Neurosci Lett 230:13–16

    PubMed  Article  CAS  Google Scholar 

  65. Stancampiano R, Cocco S, Cugusi C et al (1999) Serotonin and acetylcholine release response in the rat hippocampus during a spatial memory task. Neuroscience 89:1135–1143

    PubMed  Article  CAS  Google Scholar 

  66. Nail-Boucherie K, Dourmap N, Jaffard R et al (2000) Contextual fear conditioning is associated with an increase of acetylcholine release in the hippocampus of rat. Cogn Brain Res 9:193–197

    Article  CAS  Google Scholar 

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Acknowledgments

KER is thankful to Lumen Marketing Company (Chennai, India) for providing the standardised B. monniera extract (BESEB CDRI-08). This work was partially supported by Department of Atomic Energy through Young Scientists Program to KER (2006/20/37/3/BRNS/2377/2007) and UGC-SAP Program to Department of Animal Science. We thank Ambigapathy Ganesh for assistance with documentation.

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Correspondence to Koilmani Emmanuvel Rajan.

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Emmanuvel Rajan, K., Singh, H.K., Parkavi, A. et al. Attenuation of 1-(m-Chlorophenyl)-Biguanide Induced Hippocampus-Dependent Memory Impairment by a Standardised Extract of Bacopa monniera (BESEB CDRI-08). Neurochem Res 36, 2136 (2011). https://doi.org/10.1007/s11064-011-0538-7

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  • DOI: https://doi.org/10.1007/s11064-011-0538-7

Keywords

  • Learning and memory
  • Bacopa monniera
  • BESEB CDRI-08
  • Hippocampus
  • 5-HT receptors
  • mCPBG