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WIN55,212-2, a Dual Modulator of Cannabinoid Receptors and G Protein-Coupled Inward Rectifier Potassium Channels
Article

WIN55,212-2 Attenuates Cognitive Impairments in AlCl3 + d-Galactose-Induced Alzheimer’s Disease Rats by Enhancing Neurogenesis and Reversing Oxidative Stress

1
Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 434001, Malaysia
2
Department of Human Anatomy, College of Medical Sciences, Gombe State University, Gombe 760211, Nigeria
3
Department of Human Anatomy, Faculty of Basic Medical Sciences, University of Maiduguri, Maiduguri 600230, Nigeria
4
Faculty of Medicine, Manipal University College Malaysia (MUCM), Melaka 75150, Malaysia
*
Authors to whom correspondence should be addressed.
Academic Editor: Bruno Meloni
Biomedicines 2021, 9(9), 1270; https://doi.org/10.3390/biomedicines9091270
Received: 1 August 2021 / Revised: 28 August 2021 / Accepted: 6 September 2021 / Published: 19 September 2021
(This article belongs to the Special Issue The Therapeutic Effects of Cannabinoids in Neurodegenerative Diseases)
Neurotransmission and cognitive dysfunctions have been linked to old age disorders including Alzheimer’s disease (AD). Aluminium is a known neurotoxic metal, whereas d-galactose (d-gal) has been established as a senescence agent. WIN55,212-2 (WIN), is a potent cannabinoid agonist which partially restores neurogenesis in aged rats. The current study aimed to explore the therapeutic potentials of WIN on Aluminium chloride (AlCl3) and d-gal-induced rat models with cognitive dysfunction. Healthy male albino Wistar rats weighing between 200–250 g were injected with d-gal 60 mg/kg intra peritoneally (i.p), while AlCl3 (200 mg/kg) was orally administered once daily for 10 consecutive weeks. Subsequently, from weeks 8–11 rats were co-administered with WIN (0.5, 1 and 2 mg/kg/day) and donepezil 1 mg/kg. The cognitive functions of the rats were assessed with a Morris water maze (MWM). Furthermore, oxidative stress biomarkers; malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and neurogenesis markers: Nestin and glial fibrillary acidic protein (GFAP) were also evaluated, as well as the histology of the hippocampus. The results revealed that rats exposed to AlCl3 and d-gal alone showed cognitive impairments and marked neuronal loss (p < 0.05) in their hippocampal conus ammonis 1 (CA1). Additionally, a significant decrease in the expressions of GFAP and Nestin was also observed, including increased levels of MDA and decreased levels of SOD and GSH. However, administration of WIN irrespective of the doses given reversed the cognitive impairments and the associated biochemical derangements. As there were increases in the levels SOD, GSH, Nestin and GFAP (p < 0.05), while a significant decrease in the levels of MDA was observed, besides attenuation of the aberrant cytoarchitecture of the rat’s hippocampi. The biochemical profiles of the WIN-treated rats were normal. Thus, these findings offer possible scientific evidence of WIN being an effective candidate in the treatment of AD-related cognitive deficits. View Full-Text
Keywords: WIN55,212-2; cognitive functions; aluminium chloride; d-galactose; Alzheimer’s disease; cannabinoid; oxidative stress; neurogenesis WIN55,212-2; cognitive functions; aluminium chloride; d-galactose; Alzheimer’s disease; cannabinoid; oxidative stress; neurogenesis
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MDPI and ACS Style

Mahdi, O.; Chiroma, S.M.; Hidayat Baharuldin, M.T.; Mohd Nor, N.H.; Mat Taib, C.N.; Jagadeesan, S.; Devi, S.; Mohd Moklas, M.A. WIN55,212-2 Attenuates Cognitive Impairments in AlCl3 + d-Galactose-Induced Alzheimer’s Disease Rats by Enhancing Neurogenesis and Reversing Oxidative Stress. Biomedicines 2021, 9, 1270. https://doi.org/10.3390/biomedicines9091270

AMA Style

Mahdi O, Chiroma SM, Hidayat Baharuldin MT, Mohd Nor NH, Mat Taib CN, Jagadeesan S, Devi S, Mohd Moklas MA. WIN55,212-2 Attenuates Cognitive Impairments in AlCl3 + d-Galactose-Induced Alzheimer’s Disease Rats by Enhancing Neurogenesis and Reversing Oxidative Stress. Biomedicines. 2021; 9(9):1270. https://doi.org/10.3390/biomedicines9091270

Chicago/Turabian Style

Mahdi, Onesimus, Samaila M. Chiroma, Mohamad T. Hidayat Baharuldin, Nurul H. Mohd Nor, Che N. Mat Taib, Saravanan Jagadeesan, Shamala Devi, and Mohamad A. Mohd Moklas 2021. "WIN55,212-2 Attenuates Cognitive Impairments in AlCl3 + d-Galactose-Induced Alzheimer’s Disease Rats by Enhancing Neurogenesis and Reversing Oxidative Stress" Biomedicines 9, no. 9: 1270. https://doi.org/10.3390/biomedicines9091270

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