WIN55,212-2 Attenuates Cognitive Impairments in AlCl<sub>3</sub> + <span style="font-variant: small-caps">d</span>-Galactose-Induced Alzheimer’s Disease Rats by Enhancing Neurogenesis and Reversing Oxidative Stress
Neurotransmission and cognitive dysfunctions have been linked to old age disorders including Alzheimer’s disease (AD). Aluminium is a known neurotoxic metal, whereas <span style="font-variant: small-caps;">d</span>-galactose (<span style="font-variant: small-caps;"...
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MDPI AG
2021-09-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/9/1270 |
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| author | Onesimus Mahdi Samaila Musa Chiroma Mohamad Taufik Hidayat Baharuldin Nurul Huda Mohd Nor Che Norma Mat Taib Saravanan Jagadeesan Shamala Devi Mohamad Aris Mohd Moklas |
| author_facet | Onesimus Mahdi Samaila Musa Chiroma Mohamad Taufik Hidayat Baharuldin Nurul Huda Mohd Nor Che Norma Mat Taib Saravanan Jagadeesan Shamala Devi Mohamad Aris Mohd Moklas |
| author_sort | Onesimus Mahdi |
| collection | DOAJ |
| description | Neurotransmission and cognitive dysfunctions have been linked to old age disorders including Alzheimer’s disease (AD). Aluminium is a known neurotoxic metal, whereas <span style="font-variant: small-caps;">d</span>-galactose (<span style="font-variant: small-caps;">d</span>-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 (AlCl<sub>3</sub>) and <span style="font-variant: small-caps;">d</span>-gal-induced rat models with cognitive dysfunction. Healthy male albino Wistar rats weighing between 200–250 g were injected with <span style="font-variant: small-caps;">d</span>-gal 60 mg/kg intra peritoneally (i.p), while AlCl<sub>3</sub> (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 AlCl<sub>3</sub> and <span style="font-variant: small-caps;">d</span>-gal alone showed cognitive impairments and marked neuronal loss (<i>p</i> < 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 (<i>p</i> < 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. |
| first_indexed | 2024-03-10T07:52:14Z |
| format | Article |
| id | doaj.art-5af3bd41ed704c0f850f8de9f35659c6 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T07:52:14Z |
| publishDate | 2021-09-01 |
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| spelling | doaj.art-5af3bd41ed704c0f850f8de9f35659c62023-11-22T12:09:35ZengMDPI AGBiomedicines2227-90592021-09-0199127010.3390/biomedicines9091270WIN55,212-2 Attenuates Cognitive Impairments in AlCl<sub>3</sub> + <span style="font-variant: small-caps">d</span>-Galactose-Induced Alzheimer’s Disease Rats by Enhancing Neurogenesis and Reversing Oxidative StressOnesimus Mahdi0Samaila Musa Chiroma1Mohamad Taufik Hidayat Baharuldin2Nurul Huda Mohd Nor3Che Norma Mat Taib4Saravanan Jagadeesan5Shamala Devi6Mohamad Aris Mohd Moklas7Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 434001, MalaysiaDepartment of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 434001, MalaysiaDepartment of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 434001, MalaysiaDepartment of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 434001, MalaysiaDepartment of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 434001, MalaysiaDepartment of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 434001, MalaysiaDepartment of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 434001, MalaysiaDepartment of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 434001, MalaysiaNeurotransmission and cognitive dysfunctions have been linked to old age disorders including Alzheimer’s disease (AD). Aluminium is a known neurotoxic metal, whereas <span style="font-variant: small-caps;">d</span>-galactose (<span style="font-variant: small-caps;">d</span>-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 (AlCl<sub>3</sub>) and <span style="font-variant: small-caps;">d</span>-gal-induced rat models with cognitive dysfunction. Healthy male albino Wistar rats weighing between 200–250 g were injected with <span style="font-variant: small-caps;">d</span>-gal 60 mg/kg intra peritoneally (i.p), while AlCl<sub>3</sub> (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 AlCl<sub>3</sub> and <span style="font-variant: small-caps;">d</span>-gal alone showed cognitive impairments and marked neuronal loss (<i>p</i> < 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 (<i>p</i> < 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.https://www.mdpi.com/2227-9059/9/9/1270WIN55,212-2cognitive functionsaluminium chloride<span style="font-variant: small-caps">d</span>-galactoseAlzheimer’s diseasecannabinoid |
| spellingShingle | Onesimus Mahdi Samaila Musa Chiroma Mohamad Taufik Hidayat Baharuldin Nurul Huda Mohd Nor Che Norma Mat Taib Saravanan Jagadeesan Shamala Devi Mohamad Aris Mohd Moklas WIN55,212-2 Attenuates Cognitive Impairments in AlCl<sub>3</sub> + <span style="font-variant: small-caps">d</span>-Galactose-Induced Alzheimer’s Disease Rats by Enhancing Neurogenesis and Reversing Oxidative Stress Biomedicines WIN55,212-2 cognitive functions aluminium chloride <span style="font-variant: small-caps">d</span>-galactose Alzheimer’s disease cannabinoid |
| title | WIN55,212-2 Attenuates Cognitive Impairments in AlCl<sub>3</sub> + <span style="font-variant: small-caps">d</span>-Galactose-Induced Alzheimer’s Disease Rats by Enhancing Neurogenesis and Reversing Oxidative Stress |
| title_full | WIN55,212-2 Attenuates Cognitive Impairments in AlCl<sub>3</sub> + <span style="font-variant: small-caps">d</span>-Galactose-Induced Alzheimer’s Disease Rats by Enhancing Neurogenesis and Reversing Oxidative Stress |
| title_fullStr | WIN55,212-2 Attenuates Cognitive Impairments in AlCl<sub>3</sub> + <span style="font-variant: small-caps">d</span>-Galactose-Induced Alzheimer’s Disease Rats by Enhancing Neurogenesis and Reversing Oxidative Stress |
| title_full_unstemmed | WIN55,212-2 Attenuates Cognitive Impairments in AlCl<sub>3</sub> + <span style="font-variant: small-caps">d</span>-Galactose-Induced Alzheimer’s Disease Rats by Enhancing Neurogenesis and Reversing Oxidative Stress |
| title_short | WIN55,212-2 Attenuates Cognitive Impairments in AlCl<sub>3</sub> + <span style="font-variant: small-caps">d</span>-Galactose-Induced Alzheimer’s Disease Rats by Enhancing Neurogenesis and Reversing Oxidative Stress |
| title_sort | win55 212 2 attenuates cognitive impairments in alcl sub 3 sub span style font variant small caps d span galactose induced alzheimer s disease rats by enhancing neurogenesis and reversing oxidative stress |
| topic | WIN55,212-2 cognitive functions aluminium chloride <span style="font-variant: small-caps">d</span>-galactose Alzheimer’s disease cannabinoid |
| url | https://www.mdpi.com/2227-9059/9/9/1270 |
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