D-galactose and aluminium chloride induced rat model with cognitive impairments

被引:88
作者
Chiroma, Samaila Musa [1 ,2 ]
Moklas, Mohamad Aris Mohd [1 ]
Taib, Che Norma Mat [1 ]
Baharuldin, Mohamad Taufik Hidayat [1 ]
Amon, Zulkhairi [3 ]
机构
[1] Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Human Anat, Serdang, Selangor, Malaysia
[2] Univ Maiduguri, Coll Med Sci, Dept Human Anat, Maiduguri, Borno State, Nigeria
[3] UiTM Campus Puncak Alam, Fac Hlth Sci, Puncak Alam, Selangor, Malaysia
关键词
Alzheimer's disease; D-galactose; Aluminium chloride; Cognitive impairment; Neurodegenerative disease; Dementia; Acetylcholinesterase; Neurofibrillary tangles; Senile plaques; Beta amyloid; Alzheimerogenic chemicals; Learning dysfunction; Hyper-phosphorylated tau protein; Neurotoxins; Morris water maze; Hippocampus; Non-transgenic; Cornus ammonis; Open field test; Western blot; ALZHEIMERS-DISEASE; MEMORY IMPAIRMENT; BRAIN; DEGENERATION; HIPPOCAMPUS; APOPTOSIS; DEMENTIA; PATHWAY; PROTEIN; BURDEN;
D O I
10.1016/j.biopha.2018.04.152
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Cognitive impairments and cholinergic dysfunctions have been well reported in old age disorders including Alzheimer's disease (AD). D-galactose (D-gal) has been reported as a senescence agent while aluminium act as a neurotoxic metal, but little is known about their combined effects at different doses. The aim of this study was to establish an animal model with cognitive impairments by comparing the effects of different doses of co-administrated D-gal and aluminium chloride (AlCl3). In this study male albino wistar rats were administered with D-gal 60 mg/kg. bwt intra peritoneally (I.P) injected and AlCl3 (100, 200, or 300 mg/kg.bwt.) was orally administered once daily for 10 consecutive weeks. Performance of the rats were evaluated through behavioural assessments; Morris water maze (MWM) and open field tests (OFT); histopathological examination was performed on the hippocampus; moreover biochemical measurements of acetylcholinesterase (AChE) and hyper-phosphorylated tau protein (p-tau) were examined. The results of this experiment on rats treated with D-gal 60 + AlCl3 200 mg/kg.bwt showed near ideal cognitive impairments. The rats exhibited an obvious memory and learning deficits, marked neuronal loss in hippocampus, showed increase in AChE activities and high expression of p-tau within the tissues of the brain. This study concludes that D-gal 60 + AlCl3 200 mg/kg.bwt as the ideal dose for mimicking AD like cognitive impairments in albino wistar rats. It is also crucial to understand the pathogenesis of this neurodegenerative disease and for drug discovery.
引用
收藏
页码:1602 / 1608
页数:7
相关论文
共 46 条
[1]  
Ali AF, 2016, INTEL SYST REF LIBR, V96, P1, DOI 10.1007/978-3-319-21212-8_1
[2]   FTY720 (Fingolimod) Attenuates Beta-amyloid Peptide (Aβ42)-Induced Impairment of Spatial Learning and Memory in Rats [J].
Asle-Rousta, Masoumeh ;
Kolahdooz, Zeynab ;
Oryan, Shahrbanoo ;
Ahmadiani, Abolhassan ;
Dargahi, Leila .
JOURNAL OF MOLECULAR NEUROSCIENCE, 2013, 50 (03) :524-532
[3]   Carnosine and taurine treatments diminished brain oxidative stress and apoptosis in D-galactose aging model [J].
Aydin, A. Fatih ;
Coban, Jale ;
Dogan-Ekici, Isin ;
Betul-Kalaz, Esra ;
Dogru-Abbasoglu, Semra ;
Uysal, Mujdat .
METABOLIC BRAIN DISEASE, 2016, 31 (02) :337-345
[4]   THE IMPORTANCE OF COMPARATIVE-STUDIES AND ECOLOGICAL VALIDITY FOR UNDERSTANDING HIPPOCAMPAL STRUCTURE AND COGNITIVE FUNCTION [J].
BINGMAN, VP .
HIPPOCAMPUS, 1992, 2 (03) :213-219
[5]   Forecasting the global burden of Alzheimer's disease [J].
Brookmeyer, Ron ;
Johnson, Elizabeth ;
Ziegler-Graham, Kathryn ;
Arrighi, H. Michael .
ALZHEIMERS & DEMENTIA, 2007, 3 (03) :186-191
[6]  
Bucala R, 1992, Adv Pharmacol, V23, P1
[7]   Chronic systemic D-galactose exposure induces memory loss, neuro degeneration, and oxidative damage in mice:: Protective effects of R-α-lipoic acid [J].
Cui, Xu ;
Zuo, Pingping ;
Zhang, Qing ;
Li, Xuekun ;
Hu, Yazhuo ;
Long, Jiangang ;
Packer, Lester ;
Liu, Jiankang .
JOURNAL OF NEUROSCIENCE RESEARCH, 2006, 84 (03) :647-654
[8]   Changing patient characteristics and survival experience in an Alzheimer's center patient cohort [J].
Doody, R ;
Pavlik, V ;
Massman, P ;
Kenan, M ;
Yeh, S ;
Powell, S ;
Cooke, N ;
Dyer, C ;
Demirovic, J ;
Waring, S ;
Chan, WY .
DEMENTIA AND GERIATRIC COGNITIVE DISORDERS, 2005, 20 (2-3) :198-208
[9]  
Dumont M, 2011, METHODS MOL BIOL, V793, P229, DOI 10.1007/978-1-61779-328-8_15
[10]   THE BASAL FOREBRAIN CORTICAL CHOLINERGIC SYSTEM - INTERPRETING THE FUNCTIONAL CONSEQUENCES OF EXCITOTOXIC LESIONS [J].
DUNNETT, SB ;
EVERITT, BJ ;
ROBBINS, TW .
TRENDS IN NEUROSCIENCES, 1991, 14 (11) :494-501