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Effects of Zizyphus jujube Extract on Memory and Learning Impairment Induced by Bilateral Electric Lesions of the Nucleus Basalis of Meynert in Rat

Abstract

Alzheimer’s disease (AD) is a common neurodegenerative condition that affects the elderly population. Its primary symptom is memory loss. The memory dysfunction in AD has been associated with cortical cholinergic deficiency and loss of cholinergic neurons of the nucleus basalis of Meynert (NBM). Zizyphus jujube (ZJ) activates choline acetyltransferase and may have beneficial effects in AD patients. This study investigates the effect of ZJ extract in intact rats and in rat model of AD. 49 male Wistar rats were divided into seven equal groups (1—control, without surgery, received water), 2—AD (bilateral NBM lesion, received water), 3 and 4—AD + ZJ (NBM bilateral lesion, received ZJ extract 500 and 1,000 mg/kg b.w. per day for 15 days), 5—sham (surgery: electrode introduced into NBM without lesion, received water), 6 and 7—without surgery and lesion, received ZJ extract—the same as groups 3 and 4). The learning and memory performance were assessed using passive avoidance paradigm, and the memory cognition for spatial learning and memory was evaluated by Morris water maze. In shuttle box test ZJ extract (500 and 1,000 mg) significantly increased step-through latency in AD + ZJ groups compared with AD group. In Morris water maze test (in probe day), both AD + ZJ groups receiving extract (500 and 1,000 mg) demonstrated significant preference for the quadrant in which the platform was located on the preceding day as compared with AD group. Our results suggested that ZJ has repairing effects on memory and behavioral disorders produced by NBM lesion in rats and may have beneficial effects in treatment of AD patients.

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Abbreviations

AD:

Alzheimer’s disease

MDA:

Malondialdehyde

NBM:

Nucleus basalis of Meynert

FRAP:

Ferric reducing/antioxidant power

ZJ:

Zizyphus jujube

References

  1. 1.

    Iqbal K, Grundke-Iqbal I (2008) Alzheimer neurofibrillary degeneration: significance, etiopathogenesis, therapeutics and prevention. J Cell Mol Med 12(1):38–55

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  2. 2.

    Francis PT, Palmer AM, Snape M, Wilcock GK (1999) The cholinergic hypothesis of Alzheimer disease: a review of progress. J Neurol Neurosurg Psychiatry 66(2):137–147

    CAS  PubMed  Article  Google Scholar 

  3. 3.

    Pimplikar SW (2009) Reassessing the amyloid cascade hypothesis of Alzheimer’s disease. Int J Biochem Cell 41(6):1261–1268

    CAS  Article  Google Scholar 

  4. 4.

    Lo Conte G, Bartolini L, Casamenti F, Marconcini-Pepeu I, Pepeu G (1982) Lesions of cholinergic forebrain nuclei: changes in avoidance behavior and scopolamine actions. Pharmacol Biochem Behav 17(5):933–937

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Friedman E, Lerer B, Kuster J (1983) Loss of cholinergic neurons in the rat neocortex produces deficits in passive avoidance learning. Pharmacol Biochem Behav 19(2):309–312

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Strohmeyer R, Rogers J (2001) Molecular and cellular mediators of Alzheimer’s disease inflammation. J Alzheimers Dis 3(1):131–157

    CAS  PubMed  Google Scholar 

  7. 7.

    Lahiri DK, Farlow MR, Greig NH, Sambamurti K (2002) Current drug targets for Alzheimer’s disease treatment. Drug Develop Res 56(3):267–281

    CAS  Article  Google Scholar 

  8. 8.

    Kashani M, Tavirani M, Talaei S, Salami M (2011) Aqueous extract of lavender (Lavandula angustifolia) improves the spatial performance of a rat model of Alzheimers disease. Neurosci Bull 27(2):99–106

    PubMed  Article  Google Scholar 

  9. 9.

    Orhan I, Eener B, Choudhary MI, Khalid A (2004) Acetylcholinesterase and butyrylcholinesterase inhibitory activity of some Turkish medicinal plants. J Ethnopharmacol 91(1):57–60

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Mukherjee PK, Kumar V, Mal M, Houghton PJ (2007) Acetylcholinesterase inhibitors from plants. Phytomedicine 14(4):289–300

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Oda Y (1999) Choline acetyltransferase: the structure, distribution and pathologic changes in the central nervous system. Pathol Int 49(11):921–937

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Yatin S, Aksenov M, Butterfield DA (1999) The antioxidant vitamin E modulates amyloid peptide-induced creatine kinase activity inhibition and increased protein oxidation: implications for the free radical hypothesis of Alzheimer’s Disease. Neurochem Res 24(3):427–435

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Blazekovic B, Vladimir-Knezevic S, Brantner A, Stefan MB (2010) Evaluation of antioxidant potential of Lavandula x intermedia Emeric ex Loisel. ‘Budrovka’: a comparative study with L. angustifolia mill. Molecules 15(9):5971–5987

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Heo H-J, Park Y-J, Suh Y-M, Choi S-J, Kim M-J, Cho H-Y, Chang Y-J, Hong B, Kim H-K, Kim E, Kim C-J, Kim B-G, Shin D-H (2003) Effects of oleamide on choline acetyltransferase and cognitive activities. Biosci Biotechnol Biochem 67(6):1284–1291

    CAS  PubMed  Article  Google Scholar 

  15. 15.

    Pahuja M, Mehla J, Reeta KH, Joshi S, Gupta YK (2011) Hydroalcoholic extract of Zizyphus jujuba ameliorates seizures, oxidative stress, and cognitive impairment in experimental models of epilepsy in rats. Epilepsy Behav 21(4):356–363

    PubMed  Article  Google Scholar 

  16. 16.

    Moon JH, Terao J (1998) Antioxidant activity of caffeic acid and dihydrocaffeic acid in lard and human low-density lipoprotein. J Agric Food Chem 46:5062–5065

    CAS  Article  Google Scholar 

  17. 17.

    Folin O, Ciocalteau V (1927) On tyrosine and tryptophan determination in protein. J Biol Chem 73:627–650

    CAS  Google Scholar 

  18. 18.

    Asgari S, Setorki M, Rafieian-kopaei M, Heidarian E, Shahinfard N, Ansari R, Forouzandeh Z (2010) Postprandial hypolipidemic and hypoglycemic effects of Allium hertifolium and Sesamum indicum on hypercholesterolemic rabbits. Afr J Pharm Pharacol 15(6):1131–1135

    Google Scholar 

  19. 19.

    Paxinos G, Watson C (1997) The rat brain in stereotaxic coordinates, 3rd edn. Academic Press, San Diego

    Google Scholar 

  20. 20.

    Vale-Martnez A, Guillazo-Blanch G, Mar-Nicolovius M, Nadal R, Arvalo-Gara R, Morgado-Bernal I (2002) Electrolytic and ibotenic acid lesions of the nucleus basalis magnocellularis interrupt long-term retention, but not acquisition of two-way active avoidance, in rats. Exp Brain Res 142(1):52–66

    Article  Google Scholar 

  21. 21.

    Quervain D, Dominique JF, Roozendaal B, McGaugh JL (1998) Stress and glucocorticoids impair retrieval of long-term spatial memory. Nature 394(6695):787–790

    PubMed  Article  Google Scholar 

  22. 22.

    Khalili M, Roghani M, Ekhlasi M (2009) The effect of aqueous crocus sativus L. extract on intracerebroventricular streptozotocin-induced cognitive deficits in rat: a behavioral analysis. Iran J. Pharm Res 8(3):185–191

    Google Scholar 

  23. 23.

    Benzie IFF, Strain JJ, Lester P (1999) Ferric reducing/antioxidant power assay: direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration. Method Enzymol 299:15–27

    CAS  Google Scholar 

  24. 24.

    Karatas F, Karatepe M, Baysar A (2002) Determination of free malondialdehyde in human serum by high-performance liquid chromatography. Anal Biochem 311(1):76–79

    CAS  PubMed  Article  Google Scholar 

  25. 25.

    Nie K, Yu J-C, Fu Y, Cheng H-Y, Chen F-Y, Qu Y, Han J-X (2009) Age-related decrease in constructive activation of Akt/PKB in SAMP10 hippocampus. Biochem Biophys Res 378(1):103–107

    CAS  Article  Google Scholar 

  26. 26.

    Heinrich M, LeeTeoh H (2004) Galanthamine from snowdrop the development of a modern drug against Alzheimer disease from local Caucasian knowledge. J Ethnopharmacol 92(23):147–162

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Butt AE, Hodge GK (1997) Simple and configural association learning in rats with bilateral quisqualic acid lesions of the nucleus basalis magnocellularis. Behav Brain Res 89(12):71–85

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Lorenzini CA, Baldi E, Bucherelli C, Sacchetti B, Tassoni G (1996) Role of dorsal hippocampus in acquisition, consolidation and retrieval of rat’s passive avoidance response: a tetrodotoxin functional inactivation study. Brain Res 730:32–39

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Montero-Pastor A, Vale-Martnez A, Guillazo-Blanch G, Mart-Nicolovius M (2004) Effects of electrical stimulation of the nucleus basalis on two-way active avoidance acquisition, retention, and retrieval. Behav Brain Res 154(1):41–54

    PubMed  Article  Google Scholar 

  30. 30.

    Cahill L, McGaugh JL, Weinberger NM (2001) The neurobiology of learning and memory: some reminders to remember. Trends Neurosci 24(10):578–581

    CAS  PubMed  Article  Google Scholar 

  31. 31.

    Flicker C, Dean RL, Watkins DL, Fisher SK, Bartus RT (1983) Behavioral and neurochemical effects following neurotoxic lesions of a major cholinergic input to the cerebral cortex in the rat. Pharmacol Biochem Behav 18(6):973–981

    CAS  PubMed  Article  Google Scholar 

  32. 32.

    Nakamura S, Ishihara T (1990) Task-dependent memory loss and recovery following unilateral nucleus basalis lesion: behavioral and neurochemical correlation. Behav Brain Res 39(2):113–122

    CAS  PubMed  Article  Google Scholar 

  33. 33.

    Hasenohrl RU, Frisch C, Junghans U, Muller HW, Huston JP (1995) Facilitation of learning following injection of the chondroitin sulfate proteoglycan biglycan into the vicinity of the nucleus basalis magnocellularis. Behav Brain Res 70(1):59–67

    CAS  PubMed  Article  Google Scholar 

  34. 34.

    Sarkakai A, Amani R, Badavi M, Moghadam AZ (2008) Pretreatment effect different doses of soy isoflavones on spatial learning and memory in an ovariectomized Animal Model of Alzhimer disease. Pakistan J Biol Sci 11(8):1114–1119

    Article  Google Scholar 

  35. 35.

    Fukui K, Onodera K, Shinkai T, Suzuki S, Urano S (2001) Impairment of learning and memory in rats caused by oxidative stress and aging, and changes in antioxidative defense systems. Ann N Y Acad Sci 928(1):168–175

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    Pilz JR, Meineke I, Gleiter CH (2000) Measurement of free and bound malondialdehyde in plasma by high-performance liquid chromatography as the 2,4-dinitrophenylhydrazine derivative. J Chromatogr B 742(2):315–325

    CAS  Article  Google Scholar 

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Correspondence to Mahmoud Rafieian-kopaei.

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Rabiei, Z., Rafieian-kopaei, M., Heidarian, E. et al. Effects of Zizyphus jujube Extract on Memory and Learning Impairment Induced by Bilateral Electric Lesions of the Nucleus Basalis of Meynert in Rat. Neurochem Res 39, 353–360 (2014). https://doi.org/10.1007/s11064-013-1232-8

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Keywords

  • Zizyphus jujube
  • NBM lesioned
  • Memory impairment
  • Passive avoidance test
  • Spatial learning and memory