Skip to main content

Neuroprotective Role of Bacopa monnieri Extract in Epilepsy and Effect of Glucose Supplementation During Hypoxia: Glutamate Receptor Gene Expression

Neurochemical Research volume 33, pages 1663–1671 (2008)Cite this article

Abstract

The experiments were designed to study the glutamate gene expression during epilepsy in adult and hypoxic insult to brain during the neonatal period and the therapeutic role of neuroprotective supplements. We investigated the role of metabotropic glutamate-8 receptor (mGluR8) gene expression in cerebellum during epilepsy and neuroprotective role of Bacopa monnieri extract in epilepsy. We also studied the effect of NMDA receptor 1 (NMDAR1) gene expression during neonatal hypoxia and therapeutic role of glucose, oxygen and epinephrine supplementation. During epilepsy a significant down-regulation (P < 0.01) of mGluR8 gene expression was observed which was up-regulated (P < 0.05) near control level after B. monnieri treatment which is supported by Morris water maze experiment. In hypoxic neonates we observed up-regulation (P < 0.001) of the NMDAR1 gene expression whereas glucose and glucose + oxygen was able to significantly reverse (P < 0.001) the gene expression to near control level when compared to hypoxia and epinephrine treatment which was supported by open field test. Our results showed that B. monnieri treatment to epileptic rats significantly brought the reversal of the down-regulated mgluR8 gene expression toward control level. In neonatal rats, hypoxia induced expressional and functional changes in the NMDAR1 receptors of neuronal cells which is corrected by supplementation of glucose alone or glucose followed by oxygen during the resuscitation to prevent the glutamate related neuronal damage. Thus, the results suggest the clinical significance of corrective measures for epileptic and hypoxic management.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Jorge RE, Robinson RG, Arndt SV (1993) Are there symptoms that are specific for depressed mood in patients with traumatic brain injury? J Nerv Ment Dis 181:91–99

    Article  PubMed  CAS  Google Scholar 

  2. Van Reekum R, Cohen T, Wong J (2000) Can traumatic brain injury cause psychiatric disorders? J Neuropsychiatry Clin Neurosci 12:316–327

    PubMed  Google Scholar 

  3. McIntosh TK (1994) Neurochemical sequelae of traumatic brain injury. Cereb Brain Metab Rev 6:109–162

    CAS  Google Scholar 

  4. Olney JW (1982) The toxic effects of glutamate and related compounds in the retina and the brain. Retina 2:341–359

    Article  PubMed  CAS  Google Scholar 

  5. Caccamo D, Campisi A, Currò M et al (2004) Excitotoxic and post-ischemic neurodegeneration: involvement of transglutaminases. Amino Acids 27:373–379

    Article  PubMed  CAS  Google Scholar 

  6. Choi DW (1994) Calcium and excitotoxic neuronal injury. Ann NY Acad Sci 747:162–171

    Article  PubMed  CAS  Google Scholar 

  7. Zhang Y, Lipton P (1999) Cytosolic Ca2+changes during in vitro ischemia in rat hippocampal slices: major roles for glutamate and Na+-dependent Ca2+ release from mitochondria. J Neurosci 19:3307–3315

    PubMed  CAS  Google Scholar 

  8. Launes J, Siren J, Viinikka L et al (1998) Does glutamate mediate brain damage in acute encephalitis? Neuroreport 9:577–581

    Article  PubMed  CAS  Google Scholar 

  9. Prince HK, Conn PJ, Blackstone CD et al (1995) Down-regulation of AMPA receptor subunit GluR2 in amygdaloid kindling. J Neurochem 64:462–465

    Article  PubMed  CAS  Google Scholar 

  10. Covolan L, Smith RL, Mello LE (2000) Ultrastructural identification of dentate granule cell death from pilocarpine-induced seizures. Epilepsy Res 41:9–21

    Article  PubMed  CAS  Google Scholar 

  11. Mello LE, Cavalheiro EA, Tan AM (1993) Circuit mechanisms of seizures in the pilocarpine model of chronic epilepsy: cell loss and mossy fiber sprouting. Epilepsia 34:985–995

    Article  PubMed  CAS  Google Scholar 

  12. Kral T, Erdmann E, Sochivko D et al (2003) Downregulation of mGluR8 in pilocarpine epileptic rats. Synapse 47:278–284

    Article  PubMed  CAS  Google Scholar 

  13. Hoffman DJ, McGowan JE, Marro PJ et al (1994) Hypoxia-induced modification of the N-methyl-D-aspartate receptor in the brain of the newborn piglet. Neurosci Lett 167:156–160

    Article  PubMed  CAS  Google Scholar 

  14. Otoya RE, Seltzer AM, Donoso AO (1997) Acute and long-lasting effects of neonatal hypoxia on (+)-3-[125 I] MK-801 binding to NMDA brain receptors. Exp Neurol 148:92–99

    Article  PubMed  CAS  Google Scholar 

  15. Delivoria-Papadopoulos M, Mishra OP (1998) Mech- Delivoria anisms of cerebral injury in perinatal asphyxia and strategies for prevention. J Pediatr 132:30–34

    Article  Google Scholar 

  16. Machaalani R, Waters KA (2002) Distribution and quantification of NMDA R1 mRNA and protein in the piglet brainstem and effects of inter- mitten hypercapnic hypoxia. Brain Res 951:293–300

    Article  PubMed  CAS  Google Scholar 

  17. Glowinski J, Iversen LL (1966) Regional studies of catecholamines in the rat brain: the disposition of [3H] Norepinephrine, [3H] DOPA in various regions of the brain. J Neurochem 13:655–669

    Article  PubMed  CAS  Google Scholar 

  18. Sairam K, Dorababu M, Goel RK, Bhattacharya SK (2002) Antidepressant activity of Bacopa monniera in exprerimental models of depresson in rats. Phytomedicene 9:207–211

    Article  CAS  Google Scholar 

  19. Racine RJ (1972) Modification of seizure activity by electrical stimulation. I. After discharge threshold. Electroencephalogr Clin Neurophysiol 32:269–279

    Article  PubMed  CAS  Google Scholar 

  20. Hort J, Brozek G, Mares P et al (1999) Cognitive functions after pilocarpine-induced status epilepticus: changes during silent period precede appearance of spontaneous recurrent seizures. Epilepsia 40:1177–1183

    Article  PubMed  CAS  Google Scholar 

  21. Cannizzaro C, Martire M, Cannizzaro E et al (2001) Long lasting handling affects behavioural reactivity in adult rats of both sexes prenatally exposed to diazepam. Brain Res 904:225–233

    Article  PubMed  CAS  Google Scholar 

  22. Kitay JI (1961) Sex differences in adrenal cortical secretion in the rat. Endocrinology 68:818–824

    Article  PubMed  CAS  Google Scholar 

  23. Kandel A, Buzsaki G (1993) Cerebellar neuronal activity correlates with spike and wave EEG patterns in the rat. Epilepsy Res 16:1–9

    Article  PubMed  CAS  Google Scholar 

  24. Ruiz A, Walker MC, Fabian-Fine R et al (2004) Endogenous zinc inhibits GABA (A) receptor in a hippocampal pathway. J Neurophysiol 91:1091–1096

    Article  PubMed  CAS  Google Scholar 

  25. Jiang FL, Tang YC, Chia SC et al (2007) Anticonvulsive Effect of a Selective mGluR8 Agonist (S)-3,4-Dicarboxyphenylglycine (S-3,4- DCPG) in the Mouse Pilocarpine Model of Status Epilepticus. Epilepsia 48:783–792

    Article  PubMed  CAS  Google Scholar 

  26. Attwell PJ, Singh KN, Jane DE et al (1998) Anticonvulsant and glutamate release-inhibiting properties of the highly potent metabotropic glutamate receptor agonist (2S, 2R,3R)-2-(2,3-dicarboxycyclopropyl) glycine (DCG-IV). Brain Res 805:138–143

    Article  PubMed  CAS  Google Scholar 

  27. Gasparini F, Bruno V, Battaglia G et al (1999) (R, S)–4–phosphorno phenylglycine, a potent and selective group III metabotropic glutamate receptor agonist, is anticonvulsive and neuroprotective in vivo. J Pharmacol Exp Ther 289:1678–1687

    PubMed  CAS  Google Scholar 

  28. Morris RGM, Schenk F, Tweedie F, Jarrard LE (1990) Ibotenate lesions of hippo-campus and subiculum dissociating components of allocentric spatial learning. Eur J Neurosci 2:1016–1028

    Article  PubMed  Google Scholar 

  29. Paylor R, Rudy JW (1990) Cholinergic receptor blockade can impair the rat’s performance on both place learning and cued versions of the morris water task: the role of age and pool wall brightness. Behav Brain Res 36:79–90

    Article  PubMed  CAS  Google Scholar 

  30. Whishaw IQ, Mittleman G (1986) Visits to starts, routes, and places, by rats in swimming pool navigation tasks. J Comp Psychol 100:422–431

    Article  PubMed  CAS  Google Scholar 

  31. Okeefe J, Nadel L (1978) The Hippocampus as a Cognitive Map. Oxford University Press, Oxford

    Google Scholar 

  32. Persinger MA, Makarec K, Bradley JC (1988) Characteristics of limbic seizures evoked by peripheral injections of lithium and pilocarpine. Physiol Behav 44:27–37

    Article  PubMed  CAS  Google Scholar 

  33. Malhotra CL, Das PK (1959) Pharmacological studies of Herpestis monniera Linn. (Brahmi). Indian J Med Res 47:294–305

    PubMed  CAS  Google Scholar 

  34. Singh HK, Dhawan BN (1982) Effect of Bacopa monnieri extract on avoidance responses in rat. J Ethnopharmacol 5:205–214

    Article  PubMed  CAS  Google Scholar 

  35. Bhattacharya SK, Bhattacharya A, Kumar A (2000) Antioxidant activity of Bacopa monniera in rat frontal cortex, striatum and hippocampus. Phytother Res 14:174–179

    Article  PubMed  CAS  Google Scholar 

  36. Singh HK, Dhawan BN (1997) Neuropsychopharmacological effects of the Ayurvedic nootropic Bacopa monnieri Linn (Brahmi). Indian J Pharmachol 29:359–365

    Google Scholar 

  37. Bhattacharya SK, Kumar A, Ghosal S (1999) Effect of Bacopa monnieri on animal models of Alzheimer’s disease and perturbed central cholinergic markers of cognition in of cognition in rats. Pharmacol Toxicol 4:111–112

    Google Scholar 

  38. Singh HK, Rastogi RP, Srimal RC, Dhawan BN (1988) Effect of Bacoside A and B on the avoidance response in rats. Phyto Res 2:70–75

    Article  CAS  Google Scholar 

  39. Dhawan BN, Singh HK (1996) Pharmalogical studies on Bacopa monnieri, an ayurvedic nootropic agent. Eur Neuropsychopharmacol 6:144

    Article  Google Scholar 

  40. Rastogi S, Pal R, Kulashrestha DK (1994) Bacoside A3-A tripenoid saponin from Bacopa monniera. Phytochemistry 36:133–137

    Article  PubMed  CAS  Google Scholar 

  41. Casolini P, Zuena AR, Cinque C et al (2005) Sub-neurotoxic neonatal anoxia induces subtle behavioural changes and specific abnormalities in brain group-I metabotropic glutamate receptors in rats. J Neurochem 95:137–145

    Article  PubMed  CAS  Google Scholar 

  42. Mishra OP, Zanelli S, Ohnishi ST et al (2000) Hypoxia-induced generation of nitric oxide free radicals in cerebral cortex of newborn guinea pigs. Neurochem Res 25:1559–1565

    Article  PubMed  CAS  Google Scholar 

  43. Ho DY, Saydam TC, Fink SL et al (1995) Defective herpes simplex virus vectors expressing the rat brain glucose transporter protect cultured neurons from necrotic insults. J Neurochem 65:842–850

    Article  PubMed  CAS  Google Scholar 

  44. Lawrence MS, Sun GH, Kunis DM et al (1996) Overexpression of the glucose transporter gene with a herpes simplex viral vector protects striatal neurons against stroke. J Cereb Blood Flow Metab 16:181–185

    Article  PubMed  CAS  Google Scholar 

  45. Dash R, Lawrence M, Sapolsky R (1996) A herpes simplex virus vector overexpressing the glucose transporter gene protects the rat dentate gyrus from an antimetabolite toxin. Exp Neurol 137:43–48

    Article  PubMed  CAS  Google Scholar 

  46. Choi DW (1988) Glutamate neurotoxicity and diseases of the nervous system. Neuron 1623–1634

  47. Coyle JT, Puttfarcken P (1993) Oxidative stress, glutamate, and neurodegenerative disorders. Science 262:689–695

    Article  PubMed  CAS  Google Scholar 

  48. Li Y, Sharov VG, Jiang N et al (1998) Intact, injured, necrotic, and apoptotic cells after focal cerebral ischemia in the rat. J Neurol Sci 156:119–132

    Article  PubMed  CAS  Google Scholar 

  49. Omata N, Murata T, Fujibayashi Y et al (2000) Hypoxic but Not Ischemic Neurotoxicity of free radicals revealed by dynamic changes in glucose metabolism of fresh rat brain slices on positron autoradiography. J Cereb Blood Flow Metab 20:350–358

    Article  PubMed  CAS  Google Scholar 

  50. Hudspith MJ (1997) Glutamate a role in normal brain function, anaesthesia, analgesia and CNS injury. Br J Anaesth 78:731–747

    PubMed  CAS  Google Scholar 

  51. Rothman SM, Olney JW (1986) Glutamate and the pathophysiology of hypoxic-ischemic brain damage. Ann Neurol 19:105–11

    Article  PubMed  CAS  Google Scholar 

  52. Mar A, Spreekmeester E, Rochford J (2002) Fluoxetine-induced increases in open field habituation in the olfactory bulbectomized rat depend on test aversiveness but not on anxiety. Pharmacol Biochem Behav 73:703–712

    Article  PubMed  CAS  Google Scholar 

  53. Fedosiewicz-Wasiluk M, Hoy ZZ, Winiewska1 RJ (2005) The influence of NMDA, a potent agonist of glutamate receptor, on behavioral activity of rats with experimental hyperammonemia evoked by liver failure. Amino Acids 28:111–117

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by research grants from DBT, DST, ICMR, Govt. of India and KSCSTE, Govt. of Kerala to Dr. C. S. Paulose. Finla Chathu thanks Cochin University of Science and Technology for Junior Research Fellowship. Reas Khan thanks KSCSTE, Govt. of Kerala for Junior Research Fellowship.

Author information

Authors and Affiliations

  1. Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, Kerala, 682022, India

    C. S. Paulose, Finla Chathu, S. Reas Khan & Amee Krishnakumar

Authors
  1. C. S. Paulose
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Finla Chathu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Reas Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Amee Krishnakumar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. S. Paulose.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Paulose, C.S., Chathu, F., Reas Khan, S. et al. Neuroprotective Role of Bacopa monnieri Extract in Epilepsy and Effect of Glucose Supplementation During Hypoxia: Glutamate Receptor Gene Expression. Neurochem Res 33, 1663–1671 (2008). https://doi.org/10.1007/s11064-007-9513-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-007-9513-8

Keywords

  • Glutamate gene expression
  • Metabotropic glutamate receptor 8 (mGluR8)
  • NMDAR1
  • Neurodegeneration
  • Epilepsy
  • Hypoxia
  • Seizures
  • Bacopa monnieri
  • Glucose
  • Oxygen
  • Epinephrine
  • Cerebellum
  • Cerebral cortex
  • CT value
  • Morris water maze test and open field test