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Current Alzheimer Research

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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Research Article

Memory Enhancing and Neurogenesis Activity of Honey Bee Venom in the Symptoms of Amnesia: Using Rats with Amnesia-like Alzheimer’s Disease as a Model

Author(s): Khaled M. Khleifat, Nafe M. Al-Tawarah, Mohammad A. Al-Kafaween*, We’am Al-Ksasbeh, Haitham Qaralleh, Moath Alqaraleh, Khawla D. Al-Hamaideh, Yousef M. Al-Saraireh, Ahmad AlSarayreh, Yaseen Al Qaisi and Abu Bakar Mohd Hilmi*

Volume 20, Issue 3, 2023

Published on: 06 July, 2023

Page: [190 - 201] Pages: 12

DOI: 10.2174/1567205020666230614143027

Price: $65

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Abstract

Background/Objective: Alzheimer's disease (AD) is mainly characterized by amnesia that affects millions of people worldwide. This study aims to explore the effectiveness capacities of bee venom (BV) for the enhancement of the memory process in a rat model with amnesia-like AD.

Methods: The study protocol contains two successive phases, nootropic and therapeutic, in which two BV doses (D1; 0.25 and D2: 0.5 mg/kg i.p.) were used. In the nootropic phase, treatment groups were compared statistically with a normal group. Meanwhile, in the therapeutic phase, BV was administered to scopolamine (1mg/kg) to induce amnesia-like AD in a rat model in which therapeutic groups were compared with a positive group (donepezil; 1mg/kg i.p.). Behavioral analysis was performed after each phase by Working Memory (WM) and Long-Term Memory (LTM) assessments using radial arm maze (RAM) and passive avoidance tests (PAT). Neurogenic factors; Brain-derived neurotrophic factor (BDNF), and Doublecortin (DCX) were measured in plasma using ELISA and Immunohistochemistry analysis of hippocampal tissues, respectively.

Results: During the nootropic phase, treatment groups demonstrated a significant (P < 0.05) reduction in RAM latency times, spatial WM errors, and spatial reference errors compared with the normal group. In addition, the PA test revealed a significant (P < 0.05) enhancement of LTM after 72 hours in both treatment groups; D1 and D2. In the therapeutic phase, treatment groups reflected a significant (P < 0.05) potent enhancement in the memory process compared with the positive group; less spatial WM errors, spatial reference errors, and latency time during the RAM test, and more latency time after 72 hours in the light room. Moreover, results presented a marked increase in the plasma level of BDNF, as well as increased hippocampal DCX-positive data in the sub-granular zone within the D1 and D2 groups compared with the negative group (P < 0.05) in a dose-dependent manner.

Conclusion: This study revealed that injecting BV enhances and increases the performance of both WM and LTM. Conclusively, BV has a potential nootropic and therapeutic activity that enhances hippocampal growth and plasticity, which in turn improves WM and LTM. Given that this research was conducted using scopolamine-induced amnesia-like AD in rats, it suggests that BV has a potential therapeutic activity for the enhancement of memory in AD patients in a dose-dependent manner but further investigations are needed.

« Previous Next »
[1]
Almkvist O. Neuropsychological features of early Alzheimer’s disease: Preclinical and clinical stages. Acta Neurol Scand 1996; 94(S165): 63-71.
[http://dx.doi.org/10.1111/j.1600-0404.1996.tb05874.x] [PMID: 8740991]
[2]
Jedynak BM, Lang A, Liu B, et al. A computational neurodegenerative disease progression score: Method and results with the Alzheimer’s disease neuroimaging initiative cohort. Neuroimage 2012; 63(3): 1478-86.
[http://dx.doi.org/10.1016/j.neuroimage.2012.07.059] [PMID: 22885136]
[3]
Hajjo R, Sabbah DA, Abusara OH, Al Bawab AQ. A Review of the recent advances in Alzheimer’s Disease research and the utilization of network biology approaches for prioritizing diagnostics and therapeutics. Diagnostics 2022; 12(12): 2975.
[http://dx.doi.org/10.3390/diagnostics12122975] [PMID: 36552984]
[4]
Xie C, Miyasaka T, Yoshimura S, et al. The homologous carboxyl-terminal domains of microtubule-associated protein 2 and TAU induce neuronal dysfunction and have differential fates in the evolution of neurofibrillary tangles. PLoS One 2014; 9(2): e89796.
[http://dx.doi.org/10.1371/journal.pone.0089796] [PMID: 24587039]
[5]
Mir Z. Rosliza , Naeem B, et al. Synergistic molecular effect of BDNF, Apo E and MTHFR in inducing Depression in Alzheimer’s Disease. Res J Pharm Tech 2018; 11(10): 4317-23.
[http://dx.doi.org/10.5958/0974-360X.2018.00790.4]
[6]
Health at a Glance: Europe 2016. France: OECD Publishing Paris 2016.
[7]
Chua KK, Wong A, Kwan PWL, et al. The efficacy and safety of the Chinese herbal medicine Di-Tan decoction for treating Alzheimer’s disease: Protocol for a randomized controlled trial. Trials 2015; 16(1): 199.
[http://dx.doi.org/10.1186/s13063-015-0716-z] [PMID: 25925312]
[8]
Zhu H, Yan H, Tang N, et al. Impairments of spatial memory in an Alzheimer’s disease model via degeneration of hippocampal cholinergic synapses. Nat Commun 2017; 8(1): 1676.
[http://dx.doi.org/10.1038/s41467-017-01943-0] [PMID: 29162816]
[9]
Huntley J, Howard R. Working memory in early Alzheimer’s disease: A neuropsychological review. Int J Geriatr Psychiatry 2010; 25(2): 121-32.
[http://dx.doi.org/10.1002/gps.2314]
[10]
Mu Y, Gage FH. Adult hippocampal neurogenesis and its role in Alzheimer’s disease. Mol Neurodegener 2011; 6(1): 85.
[http://dx.doi.org/10.1186/1750-1326-6-85] [PMID: 22192775]
[11]
Singhal A, Bangar OP, Naithani V. Medicinal plants with a potential to treat Alzheimer and associated symptoms. Int J Nutr Pharmacol Neurol Dis 2012; 2(2): 84.
[http://dx.doi.org/10.4103/2231-0738.95927]
[12]
Bathina S, Das UN. Brain-derived neurotrophic factor and its clinical implications. Arch Med Sci 2015; 6(6): 1164-78.
[http://dx.doi.org/10.5114/aoms.2015.56342] [PMID: 26788077]
[13]
Pinton S, Sampaio TB, Savall AS, Gutierrez MEZ. Neurotrophic factors in Alzheimer’s and Parkinson’s diseases: Implications for pathogenesis and therapy. Neural Regen Res 2017; 12(4): 549-57.
[http://dx.doi.org/10.4103/1673-5374.205084] [PMID: 28553325]
[14]
Mohd Sairazi NS, Sirajudeen K. Natural products and their bioactive compounds: Neuroprotective potentials against neurodegenerative diseases. Evid Based Complement Alternat Med 2020; 2020: 6565396.
[http://dx.doi.org/10.1155/2020/6565396]
[15]
Khalaf-Nazzal R, Stouffer MA, Olaso R, et al. Early born neurons are abnormally positioned in the doublecortin knockout hippocampus. Hum Mol Genet 2017; 26(1): 90-108.
[PMID: 28007902]
[16]
Encinas JM, Sierra A. Neural stem cell deforestation as the main force driving the age-related decline in adult hippocampal neurogenesis. Behav Brain Res 2012; 227(2): 433-9.
[http://dx.doi.org/10.1016/j.bbr.2011.10.010] [PMID: 22019362]
[17]
Lipsky RH, Marini AM. Brain-derived neurotrophic factor in neuronal survival and behavior-related plasticity. Ann N Y Acad Sci 2007; 1122(1): 130-43.
[http://dx.doi.org/10.1196/annals.1403.009] [PMID: 18077569]
[18]
Wilkinson DG, Francis PT, Schwam E, Payne-Parrish J. Cholinesterase inhibitors used in the treatment of Alzheimer’s disease: The relationship between pharmacological effects and clinical efficacy. Drugs Aging 2004; 21(7): 453-78.
[http://dx.doi.org/10.2165/00002512-200421070-00004] [PMID: 15132713]
[19]
Birks JS. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev 2006; 2006(1): CD005593.
[http://dx.doi.org/10.1002/14651858.CD005593]
[20]
A Al-Kafaween M, Mohd Hilmi AB, A Nagi Al-Jamal H, A Elsahoryi N, Jaffar N, Khairi Zahri M. Pseudomonas aeruginosa and Streptococcus pyogenes exposed to Malaysian trigona honey in vitro demonstrated downregulation of virulence factor. Iran J Biotechnol 2020; 18(4): e2542.
[PMID: 34056021]
[21]
Stawiarz E, Dyduch J. The use of honey bee products of plant origin in apitherapy. Episteme 2014; 25: 111-27.
[22]
Hammad AM, Ibrahim YA, Khdair SI, et al. Metformin reduces oxandrolone- induced depression-like behavior in rats via modulating the expression of IL-1β IL-6, IL-10 and TNF-α. Behav Brain Res 2021; 414: 113475.
[http://dx.doi.org/10.1016/j.bbr.2021.113475] [PMID: 34280460]
[23]
Alkafaween MA, Kafaween H, Al-Groom RM. A comparative study of antibacterial activity of Citrus and Jabali Honeys with Manuka Honey. Appl Environ Biotechnol 2022; 7(1): 28-37.
[http://dx.doi.org/10.26789/AEB.2022.01.004]
[24]
Yang EJ, Jiang JH, Lee SM, et al. Bee venom attenuates neuroinflammatory events and extends survival in amyotrophic lateral sclerosis models. J Neuroinflammation 2010; 7(1): 69.
[http://dx.doi.org/10.1186/1742-2094-7-69] [PMID: 20950451]
[25]
Lee VMY, Goedert M, Trojanowski JQ. Neurodegenerative Tauopathies. Annu Rev Neurosci 2001; 24(1): 1121-59.
[http://dx.doi.org/10.1146/annurev.neuro.24.1.1121] [PMID: 11520930]
[26]
Kim JI, Yang EJ, Lee MS, et al. Bee venom reduces neuroinflammation in the MPTP-induced model of Parkinson’s disease. Int J Neurosci 2011; 121(4): 209-17.
[http://dx.doi.org/10.3109/00207454.2010.548613] [PMID: 21265705]
[27]
Al-kafaween MA, Hilmi ABM, Al-Jamal HAN, Al-Groom RM, Elsahoryi NA, Al-Sayyed H. Potential antibacterial activity of Yemeni Sidr Honey against Pseudomonas aeruginosa and Streptococcus pyogenes. Antiinfect Agents 2021; 19(4): e130621192336.
[http://dx.doi.org/10.2174/2211352519666210319100204]
[28]
Al-kafaween MA, Al-Jamal HAN. A comparative study of antibacterial and antivirulence activities of four selected honeys to Manuka honey. Iran J Microbiol 2022; 14(2): 238-51.
[http://dx.doi.org/10.18502/ijm.v14i2.9193] [PMID: 35765547]
[29]
Bhuvanendran S, Kumari Y, Othman I, Shaikh MF. Amelioration of cognitive deficit by embelin in a scopolamine-induced Alzheimer’s disease-like condition in a rat model. Front Pharmacol 2018; 9: 665.
[http://dx.doi.org/10.3389/fphar.2018.00665] [PMID: 29988493]
[30]
Yadang FSA, Nguezeye Y, Kom CW, Betote PHD, Mamat A, Tchokouaha LRY, et al. Scopolamine-Induced Memory Impairment in Mice: Neuroprotective Effects of Carissa edulis (Forssk.) Valh (Apocynaceae). Aqueous Extract Int J Alzheimers Dis 2020; 2020: 6372059.
[31]
Hsieh MT, Wu CR, Chen CF. Gastrodin and p-hydroxybenzyl alcohol facilitate memory consolidation and retrieval, but not acquisition, on the passive avoidance task in rats. J Ethnopharmacol 1997; 56(1): 45-54.
[http://dx.doi.org/10.1016/S0378-8741(96)01501-2] [PMID: 9147253]
[32]
Rush DK. Scopolamine amnesia of passive avoidance: A deficit of information acquisition. Behav Neural Biol 1988; 50(3): 255-74.
[http://dx.doi.org/10.1016/S0163-1047(88)90938-7] [PMID: 3202811]
[33]
Olton DS. The radial arm maze as a tool in behavioral pharmacology. Physiol Behav 1987; 40(6): 793-7.
[http://dx.doi.org/10.1016/0031-9384(87)90286-1] [PMID: 3313453]
[34]
Olton DS, Collison C, Werz MA. Spatial memory and radial arm maze performance of rats. Learn Motiv 1977; 8(3): 289-314.
[http://dx.doi.org/10.1016/0023-9690(77)90054-6]
[35]
Bolhuis JJ, Bijlsma S, Ansmink P. Exponential decay of spatial memory of rats in a radial maze. Behav Neural Biol 1986; 46(2): 115-22.
[http://dx.doi.org/10.1016/S0163-1047(86)90584-4] [PMID: 3767826]
[36]
Brown MF. Does a cognitive map guide choices in the radial-arm maze? J Exp Psychol Anim Behav Process 1992; 18(1): 56-66.
[http://dx.doi.org/10.1037/0097-7403.18.1.56] [PMID: 1578200]
[37]
Batool Z, Sadir S, Liaquat L, et al. Repeated administration of almonds increases brain acetylcholine levels and enhances memory function in healthy rats while attenuates memory deficits in animal model of amnesia. Brain Res Bull 2016; 120: 63-74.
[http://dx.doi.org/10.1016/j.brainresbull.2015.11.001] [PMID: 26548495]
[38]
Haider S, Saleem S, Perveen T, et al. Age-related learning and memory deficits in rats: Role of altered brain neurotransmitters, acetylcholinesterase activity and changes in antioxidant defense system. Age 2014; 36(3): 9653.
[http://dx.doi.org/10.1007/s11357-014-9653-0] [PMID: 24771014]
[39]
Bannerman DM, Sprengel R, Sanderson DJ, et al. Hippocampal synaptic plasticity, spatial memory and anxiety. Nat Rev Neurosci 2014; 15(3): 181-92.
[http://dx.doi.org/10.1038/nrn3677] [PMID: 24552786]
[40]
Shojaei S, Panjehshahin MR, Shafiee SM, et al. Differential effects of resveratrol on the expression of brain-derived neurotrophic factor transcripts and protein in the hippocampus of rat brain. Iran J Med Sci 2017; 42(1): 32-9.
[PMID: 28293048]
[41]
Al-saraireh YM, Alshammari FOFO, Youssef AMM, et al. Cytochrome 4Z1 expression is associated with unfavorable survival in triple-negative breast cancers. Breast Cancer 2021; 13: 565-74.
[http://dx.doi.org/10.2147/BCTT.S329770] [PMID: 34675653]
[42]
Alshammari FOFO, Al-saraireh YM, Youssef AMM, Al-Sarayra YM, Alrawashdeh HM. Cytochrome P450 1B1 overexpression in cervical cancers: Cross-sectional study. Interact J Med Res 2021; 10(4): e31150.
[http://dx.doi.org/10.2196/31150] [PMID: 34636736]
[43]
Yamashima T, Popivanova BK, Guo J, et al. Implication of “Down syndrome cell adhesion molecule” in the hippocampal neurogenesis of ischemic monkeys. Hippocampus 2006; 16(11): 924-35.
[http://dx.doi.org/10.1002/hipo.20223] [PMID: 16983647]
[44]
Zurier RB, Mitnick H, Bloomgarden D, Weissmann G. Effect of bee venom on experimental arthritis. Ann Rheum Dis 1973; 32(5): 466-70.
[http://dx.doi.org/10.1136/ard.32.5.466] [PMID: 4751783]
[45]
Cai M, Lee JH, Yang EJ. Bee venom ameliorates cognitive dysfunction caused by neuroinflammation in an animal model of vascular dementia. Mol Neurobiol 2017; 54(8): 5952-60.
[http://dx.doi.org/10.1007/s12035-016-0130-x] [PMID: 27686075]
[46]
Singh AK, Rai SN, Maurya A, Mishra G, Awasthi R, Shakya A, et al. Therapeutic potential of phytoconstituents in management of Alzheimer’s disease. Evid Based Complement Alternat Med 2021; 2021: 5578574.
[http://dx.doi.org/10.1155/2021/5578574]
[47]
Chung ES, Kim H, Lee G, Park S, Kim H, Bae H. Neuro-protective effects of bee venom by suppression of neuroinflammatory responses in a mouse model of Parkinson’s disease: Role of regulatory T cells. Brain Behav Immun 2012; 26(8): 1322-30.
[http://dx.doi.org/10.1016/j.bbi.2012.08.013] [PMID: 22974722]
[48]
Nishizaki T, Matsuoka T, Nomura T, et al. A ‘long-term-potentiation-like’ facilitation of hippocampal synaptic transmission induced by the nootropic nefiracetam. Brain Res 1999; 826(2): 281-8.
[http://dx.doi.org/10.1016/S0006-8993(99)01312-8] [PMID: 10224305]
[49]
Shin J, Kong C, Lee J, et al. Focused ultrasound-induced blood-brain barrier opening improves adult hippocampal neurogenesis and cognitive function in a cholinergic degeneration dementia rat model. Alzheimers Res Ther 2019; 11(1): 110.
[http://dx.doi.org/10.1186/s13195-019-0569-x] [PMID: 31881998]
[50]
Kwon YB, Han HJ, Beitz AJ, Lee JH. Bee venom acupoint stimulation increases Fos expression in catecholaminergic neurons in the rat brain. Mol Cells 2004; 17(2): 329-3.

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