A comparative study of scopolamine, D-Galactose and AlCl3-induced Alzheimer’s like disease by enhancing hippocampal neurodegeneration and memory impairment in male rats
DOI:
https://doi.org/10.21271/ZJPAS.35.3.19Keywords:
Alzheimer’s disease, hippocampus, memory impairment, AlCl3Abstract
Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder identified by progressive loss of neurons, cognition decline, and memory deficits. The current study sought out to compare the effects of scopolamine (SCO), D-galactose (D-gala), and aluminium chloride (AlCl3) on memory performance, histological alterations of the hippocampus, and to determine the best model for inducing Alzheimer’s-like disease. Twenty-four male adult albino rats (250–300g) were used in this study, which were arbitrarily assigned into four groups: control group (normal saline), SCO group (2 mg/kg), D-gala group (125 mg/kg) and AlCl3 group (50 mg/kg). The chemicals were given intraperitoneally for 30 days. All the rats were subjected to novel object recognition (NOR) and Barnes maze (BM) tests to assess memory performance. At the end of the period, all the rats were anesthetized, blood samples were taken for hematological and biochemical tests, and the brains were removed for morphometric analysis. The results have demonstrated that SCO, D-gala, and AlCl3 caused memory impairment in BM and NOR tests, and malondialdehyde (MDA) serum levels significantly increased. Histological analysis showed degenerative pyknotic cells in the rat hippocampus. The impairment in memory performance and histopathological alterations were higher in the AlCl3 than in the other models, but the hematological parameters were significantly changed. Therefore, it was concluded that SCO (2 mg/kg) is the best model for mimicking AD-like disease among D-gala and AlCl3 by enhancing histopathological alternations and declining memory in rats without affecting other study parameters.
References
ABD-EL-FATTAH, M. A., ABDELAKADER, N. F. & ZAKI, H. F. 2014. Pyrrolidine dithiocarbamate protects against scopolamine-induced cognitive impairment in rats. Eur J Pharmacol, 723, 330-8.
ABOELWAFA, H. R., EL-KOTT, A. F., ABD-ELLA, E. M. & YOUSEF, H. N. 2020. The Possible Neuroprotective Effect of Silymarin against Aluminum Chloride-Prompted Alzheimer's-Like Disease in Rats. Brain Sci, 10.
ABULFADL, Y. S., EL-MARAGHY, N. N., AHMED, A. A. E., NOFAL, S. & BADARY, O. A. 2018. Protective effects of thymoquinone on D-galactose and aluminum chloride induced neurotoxicity in rats: biochemical, histological and behavioral changes. Neurol Res, 40, 324-333.
ADEDOSU, O., ADELEKE, G., ALAO, T., OJUGO, N. & AKINSOJI, O. 2018. Effects of vitamin E administration on certain biochemical and antioxidants indices in some rat tissues treated with aluminium chloride. Annual Research & Review in Biology, 1-13.
ALAM, M. A. & BANSAL, G. 2020. Effects of Insulin against Aluminium Induced Neurotoxicity in Wistar Rats. Pharmacology and Clinical Pharmacy Research, 5, 62-71.
ALGHAMDI, B. S. A. 2018. Possible prophylactic anti-excitotoxic and anti-oxidant effects of virgin coconut oil on aluminium chloride-induced Alzheimer's in rat models. J Integr Neurosci, 17, 593-607.
ALJARARI, R. & BAWAZIR, A. 2019. Effect of Black Raisins (Vitis vinifera) on Aluminum Chloride Induced Alzheimer's Disease in Male Albino Rat. International Journal of Pharmaceutical Research & Allied Sciences, 8.
ALSEMEH, A. E., IBRAHIM, A. A. S. & MOHAMMED, H. O. 2020. Structural and Behavioural Changes in Rat Hippocampus Induced by Methotrexate and The potential ameliorative Effect of Alpha lipoic acid. Egyptian Journal of Histology, 43, 301-324.
ALY, H., ELRIGAL, N., ALI, S., RIZK, M. & EBRAHIM, N. 2018. Modulatory effects of Casimiroa edulis on aluminium nanoparticles-associated neurotoxicity in a rat model of induced Alzheimer's disease. J. Mater. Environ. Sci, 9, 1931-1941.
AZIZ, I. A. & ZABUT, B. M. 2011. Determination of blood indices of albino rats treated with aluminum chloride and investigation of antioxidant effects of vitamin E and C. Egyptian Journal of Biology, 13, 1-7.
BARNES, C. A. 1979. Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat. J Comp Physiol Psychol, 93, 74-104.
BATOOL, Z., SADIR, S., LIAQUAT, L., TABASSUM, S., MADIHA, S., RAFIQ, S., TARIQ, S., BATOOL, T. S., SALEEM, S., NAQVI, F., PERVEEN, T. & HAIDER, S. 2016. 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, 120, 63-74.
BOCCARA, C. N., KJONIGSEN, L. J., HAMMER, I. M., BJAALIE, J. G., LEERGAARD, T. B. & WITTER, M. P. 2015. A three-plane architectonic atlas of the rat hippocampal region. Hippocampus, 25, 838-57.
BRENNAN, P. P., STANDRING, S. & WISEMAN, S. 2019. Gray's surgical anatomy e-book, Elsevier Health Sciences.
BUDZYNSKA, B., BOGUSZEWSKA-CZUBARA, A., KRUK-SLOMKA, M., SKALICKA-WOZNIAK, K., MICHALAK, A., MUSIK, I. & BIALA, G. 2015. Effects of imperatorin on scopolamine-induced cognitive impairment and oxidative stress in mice. Psychopharmacology (Berl), 232, 931-42.
CAO, Z., WANG, F., XIU, C., ZHANG, J. & LI, Y. 2017. Hypericum perforatum extract attenuates behavioral, biochemical, and neurochemical abnormalities in Aluminum chloride-induced Alzheimer's disease rats. Biomed Pharmacother, 91, 931-937.
CHAVALI, V. D., AGARWAL, M., VYAS, V. K. & SAXENA, B. 2020. Neuroprotective Effects of Ethyl Pyruvate against Aluminum Chloride-Induced Alzheimer's Disease in Rats via Inhibiting Toll-Like Receptor 4. J Mol Neurosci, 70, 836-850.
CHIROMA, S. M., BAHARULDIN, M. T. H., MAT TAIB, C. N., AMOM, Z., JAGADEESAN, S., ILHAM ADENAN, M., MAHDI, O. & MOKLAS, M. A. M. 2019. Centella asiatica protects d-galactose/AlCl3 mediated Alzheimer’s disease-like rats via PP2A/GSK-3β signaling pathway in their Hippocampus. International journal of molecular sciences, 20, 1871.
COLOMINA, M. T. & PERIS-SAMPEDRO, F. 2017. Aluminum and Alzheimer's Disease. Adv Neurobiol, 18, 183-197.
F EWIDA, S. & A MANSOUR, M. 2015. the antioxidant metabolic protective effect of exercise on d-galactose induced spatial memory impairment; possible role of hippocampal astrocytes. Al-Azhar Medical Journal, 44, 295-316.
FAWZI, S. F., MENZE, E. T. & TADROS, M. G. 2020. Deferiprone ameliorates memory impairment in Scopolamine-treated rats: The impact of its iron-chelating effect on β-amyloid disposition. Behav Brain Res, 378, 112314.
FERREIRA, M. E. S., DE VASCONCELOS, A. S., DA COSTA VILHENA, T., DA SILVA, T. L., DA SILVA BARBOSA, A., GOMES, A. R. Q., DOLABELA, M. F. & PERCÁRIO, S. 2015. Oxidative stress in Alzheimer’s disease: should we keep trying antioxidant therapies? Cellular and molecular neurobiology, 35, 595-614.
FIRDAUS, Z., SINGH, N., PRAJAPATI, S. K., KRISHNAMURTHY, S. & SINGH, T. D. 2022. Centella asiatica prevents D-galactose-Induced cognitive deficits, oxidative stress and neurodegeneration in the adult rat brain. Drug Chem Toxicol, 45, 1417-1426.
FUJI, T., INOUE, T. & HASEGAWA, Y. 2018. Nacre extract prevents scopolamine-induced memory deficits in rodents. Asian Pacific Journal of Tropical Medicine, 11, 202.
GAWEL, K., GIBULA, E., MARSZALEK-GRABSKA, M., FILAROWSKA, J. & KOTLINSKA, J. H. 2019. Assessment of spatial learning and memory in the Barnes maze task in rodents-methodological consideration. Naunyn Schmiedebergs Arch Pharmacol, 392, 1-18.
GHANBARI, A., VAFAEI, A. A., ATTARMOGHADDAM, M., BANDEGI, A. & MORADI-KOR, N. 2019. Spirulina microalgae improves memory deficit induced by scopolamine in male pup rats: Role of oxidative stress. South African Journal of Botany, 127, 220-225.
HAFEZ, H. S., GHAREEB, D. A., SALEH, S. R., ABADY, M. M., EL DEMELLAWY, M. A., HUSSIEN, H. & ABDEL-MONEM, N. 2017. Neuroprotective effect of ipriflavone against scopolamine-induced memory impairment in rats. Psychopharmacology (Berl), 234, 3037-3053.
HANSSON, O., ZETTERBERG, H., BUCHHAVE, P., LONDOS, E., BLENNOW, K. & MINTHON, L. 2006. Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol, 5, 228-34.
HARANDI, S., GOLCHIN, L., ANSARI, M., MORADI, A., SHABANI, M. & SHEIBANI, V. 2015. Antiamnesic Effects of Walnuts Consumption on Scopolamine-Induced Memory Impairments in Rats. Basic Clin Neurosci, 6, 91-9.
HEO, Y. M., SHIN, M. S., KIM, S. H., KIM, T. W., BAEK, S. B. & BAEK, S. S. 2014. Treadmill exercise ameliorates disturbance of spatial learning ability in scopolamine-induced amnesia rats. J Exerc Rehabil, 10, 155-61.
IMBIMBO, B. P., LOMBARD, J. & POMARA, N. 2005. Pathophysiology of Alzheimer's disease. Neuroimaging Clin N Am, 15, 727-53, ix.
INAN-EROGLU, E. & AYAZ, A. 2018. Is aluminum exposure a risk factor for neurological disorders? J Res Med Sci, 23, 51.
JUSTIN-THENMOZHI, A., DHIVYA BHARATHI, M., KIRUTHIKA, R., MANIVASAGAM, T., BORAH, A. & ESSA, M. M. 2018. Attenuation of Aluminum Chloride-Induced Neuroinflammation and Caspase Activation Through the AKT/GSK-3β Pathway by Hesperidin in Wistar Rats. Neurotox Res, 34, 463-476.
KANDİŞ, S., ALTINTAŞ, L., KIZILDAĞ, S., SIMSEK, F., ATEŞ, M., ALACAM, H. & UYSAL HARZADIN, N. 2022. Comparison anti-oxidant and neuroprotective effects of extra-virgin olive oil, donepezil and rosmarinic acid on aluminum chloride-induced Alzheimer's in rat models. ANKARA UNIVERSITESI VETERINER FAKULTESI DERGISI, 69.
KARRAN, E. & DE STROOPER, B. 2016. The amyloid cascade hypothesis: are we poised for success or failure? J Neurochem, 139 Suppl 2, 237-252.
KIM, M. H., KIM, S. H. & YANG, W. M. 2014. Mechanisms of action of phytochemicals from medicinal herbs in the treatment of Alzheimer's disease. Planta Med, 80, 1249-58.
KLOTZ, K., WEISTENHÖFER, W., NEFF, F., HARTWIG, A., VAN THRIEL, C. & DREXLER, H. 2017. The Health Effects of Aluminum Exposure. Dtsch Arztebl Int, 114, 653-659.
KNIERIM, J. J. 2015. The hippocampus. Current Biology, 25, R1116-R1121.
KNOPMAN, D. S., AMIEVA, H., PETERSEN, R. C., CHÉTELAT, G., HOLTZMAN, D. M., HYMAN, B. T., NIXON, R. A. & JONES, D. T. 2021. Alzheimer disease. Nature reviews Disease primers, 7, 1-21.
KOU, X., LI, J., LIU, X., YANG, X., FAN, J. & CHEN, N. 2017. Ampelopsin attenuates the atrophy of skeletal muscle from d-gal-induced aging rats through activating AMPK/SIRT1/PGC-1α signaling cascade. Biomedicine & Pharmacotherapy, 90, 311-320.
KUMAR, A., PRAKASH, A. & DOGRA, S. 2011. Centella asiatica attenuates D-galactose-induced cognitive impairment, oxidative and mitochondrial dysfunction in mice. International journal of Alzheimer’s disease, 2011.
KUMAR, A., SIDHU, J., GOYAL, A. & TSAO, J. W. 2018. Alzheimer disease.
LI, R., HUANG, Z., LUO, J., LUO, H. & WANG, W. 2020. Downregulation of the CB1-Mediated Endocannabinoid Signaling Underlies D-Galactose-Induced Memory Impairment. Frontiers in Molecular Neuroscience, 13.
LIVINGSTON, G., HUNTLEY, J., SOMMERLAD, A., AMES, D., BALLARD, C., BANERJEE, S., BRAYNE, C., BURNS, A., COHEN-MANSFIELD, J. & COOPER, C. 2020. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet, 396, 413-446.
MAT NURI, T. H., HONG, Y. H., MING, L. C., MOHD JOFFRY, S., OTHMAN, M. F. & NEOH, C. F. 2017. Knowledge on Alzheimer's Disease among Public Hospitals and Health Clinics Pharmacists in the State of Selangor, Malaysia. Front Pharmacol, 8, 739.
MAYA, S., PRAKASH, T., MADHU, K. D. & GOLI, D. 2016. Multifaceted effects of aluminium in neurodegenerative diseases: A review. Biomedicine & Pharmacotherapy, 83, 746-754.
NAM, S. M., KIM, J. W., YOO, D. Y., KIM, W., JUNG, H. Y., CHOI, J. H., HWANG, I. K., SEONG, J. K. & YOON, Y. S. 2016. Effects of aluminum on the reduction of neural stem cells, proliferating cells, and differentiating neuroblasts in the dentate gyrus of D-galactose-treated mice via increasing oxidative stress. J Vet Sci, 17, 127-36.
NEWAIRY, A. S., SALAMA, A. F., HUSSIEN, H. M. & YOUSEF, M. I. 2009. Propolis alleviates aluminium-induced lipid peroxidation and biochemical parameters in male rats. Food Chem Toxicol, 47, 1093-8.
OGUNLADE, B., ADELAKUN, S. A. & AGIE, J. A. 2022. Nutritional supplementation of gallic acid ameliorates Alzheimer-type hippocampal neurodegeneration and cognitive impairment induced by aluminum chloride exposure in adult Wistar rats. Drug Chem Toxicol, 45, 651-662.
OHKAWA, H., OHISHI, N. & YAGI, K. 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical biochemistry, 95, 351-358.
PADURARIU, M., CIOBICA, A., MAVROUDIS, I., FOTIOU, D. & BALOYANNIS, S. 2012. Hippocampal neuronal loss in the CA1 and CA3 areas of Alzheimer's disease patients. Psychiatr Danub, 24, 152-8.
PATTANASHETTI, L. A., TARANALLI, A. D., PARVATRAO, V., MALABADE, R. H. & KUMAR, D. 2017. Evaluation of neuroprotective effect of quercetin with donepezil in scopolamine-induced amnesia in rats. Indian Journal of Pharmacology, 49, 60.
RAVI, S. K., RAMESH, B. N., MUNDUGARU, R. & VINCENT, B. 2018. Multiple pharmacological activities of Caesalpinia crista against aluminium-induced neurodegeneration in rats: Relevance for Alzheimer’s disease. Environmental toxicology and pharmacology, 58, 202-211.
RETINASAMY, T., SHAIKH, M. F., KUMARI, Y. & OTHMAN, I. 2019. Ethanolic Extract of Orthosiphon stamineus Improves Memory in Scopolamine-Induced Amnesia Model. Front Pharmacol, 10, 1216.
SAEED, A., QUSTI, S. Y., ALMARWANI, R. H., JAMBI, E. J., ALSHAMMARI, E. M., GUSTY, N. F. & BALGOON, M. J. 2021. Effects of aluminum chloride and coenzyme Q10 on the molecular structure of lipids and the morphology of the brain hippocampus cells. RSC Adv, 11, 29925-29933.
SAENNO, R., DORNLAKORN, O., ANOSRI, T., KAEWNGAM, S., SIRICHOAT, A., ARANAROCHANA, A., PANNANGRONG, W., WIGMORE, P. & WELBAT, J. U. 2022. Caffeic Acid Alleviates Memory and Hippocampal Neurogenesis Deficits in Aging Rats Induced by D-Galactose. Nutrients, 14.
SAHRAEI, H., ASKARIPOUR, M., ESMAEILPOUR, K., SHAHSAVARI, F., RAJABI, S. & MORADI-KOR, N. 2019. GABA(B) receptor activation ameliorates spatial memory impairments in stress-exposed rats. Neuropsychiatr Dis Treat, 15, 1497-1506.
SHWE, T., PRATCHAYASAKUL, W., CHATTIPAKORN, N. & CHATTIPAKORN, S. C. 2018. Role of D-galactose-induced brain aging and its potential used for therapeutic interventions. Exp Gerontol, 101, 13-36.
SINGH, N. A., BHARDWAJ, V., RAVI, C., RAMESH, N., MANDAL, A. K. A. & KHAN, Z. A. 2018. EGCG Nanoparticles Attenuate Aluminum Chloride Induced Neurobehavioral Deficits, Beta Amyloid and Tau Pathology in a Rat Model of Alzheimer's Disease. Front Aging Neurosci, 10, 244.
TAMIZHAZHAGAN, V. & PUGAZHENDY, K. 2017. Histological methods in life science. International Journal of Biomedical Materials Research, 5, 68.
UGBAJA, R. N., OLANIYAN, T. O., AFOLABI, O. K., ONUNKWOR, B. O., DOSUMU, O. A., AKINHANMI, T. F., TIAMIYU, A. Y. & ALIYU-BANJO, N. O. 2017. Ionoregulatory Disruption and Acetylcholinesterase Activity in Aluminium Toxicity: Effects of Vitamins C and E. Niger J Physiol Sci, 32, 207-212.
UM, Y. H., CHOI, W. H., JUNG, W. S., PARK, Y. H., LEE, C. U. & LIM, H. K. 2017. A Case Report of a 37-Year-Old Alzheimer's Disease Patient with Prominent Striatum Amyloid Retention. Psychiatry Investig, 14, 521-524.
VLASSARA, H., BUCALA, R. & STRIKER, L. 1994. Pathogenic effects of advanced glycosylation: biochemical, biologic, and clinical implications for diabetes and aging. Lab Invest, 70, 138-51.
WANG, C., SHEN, Z., YU, J., YANG, J., MENG, F., JIANG, X. & ZHU, C. 2020. Protective effects of enzyme degradation extract from Porphyra yezoensis against oxidative stress and brain injury in D-galactose-induced ageing mice. Br J Nutr, 123, 975-986.
WONG-GUERRA, M., JIMÉNEZ-MARTIN, J., PARDO-ANDREU, G. L., FONSECA-FONSECA, L. A., SOUZA, D. O., DE ASSIS, A. M., RAMIREZ-SANCHEZ, J., DEL VALLE, R. M. & NUÑEZ-FIGUEREDO, Y. 2017. Mitochondrial involvement in memory impairment induced by scopolamine in rats. Neurol Res, 39, 649-659.
WU, C., YANG, L., TUCKER, D., DONG, Y., ZHU, L., DUAN, R., LIU, T. C.-Y. & ZHANG, Q. 2018. Beneficial effects of exercise pretreatment in a sporadic Alzheimer’s rat model. Medicine and science in sports and exercise, 50, 945.
XU, D. L., XU, M. M. & WANG, D. H. 2019. Effect of temperature on antioxidant defense and innate immunity in Brandt's voles. Zool Res, 40, 305-316.
YAKUBU, O. E., NWODO, O., IMO, C. & OGWONI, H. 2017. Spermatogenic and haematological effects of aqueous and ethanolic extracts of hymenocardiaacida stem bark on aluminiuminduced toxicity in male wistar rats. Insights in Biomedicine, 2, 1-5.
YANG, M. H., CHEN, S. C., LIN, Y. F., LEE, Y. C., HUANG, M. Y., CHEN, K. C., WU, H. Y., LIN, P. C., GOZES, I. & TYAN, Y. C. 2019. Reduction of aluminum ion neurotoxicity through a small peptide application - NAP treatment of Alzheimer's disease. J Food Drug Anal, 27, 551-564.
YIN, Y. Y., LIU, H., CONG, X. B., LIU, Z., WANG, Q., WANG, J. Z. & ZHU, L. Q. 2010. Acetyl-L-carnitine attenuates okadaic acid induced tau hyperphosphorylation and spatial memory impairment in rats. J Alzheimers Dis, 19, 735-46.
ZHANG, J., TUCKER, L. D., DONGYAN, LU, Y., YANG, L., WU, C., LI, Y. & ZHANG, Q. 2018. Tert-butylhydroquinone post-treatment attenuates neonatal hypoxic-ischemic brain damage in rats. Neurochem Int, 116, 1-12.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Bnar Rasul Abdulrahman, Zana Rafiq Majeed
This work is licensed under a Creative Commons Attribution 4.0 International License.
