Melatonin and Hydrogen Sulfide ameliorates cognitive impairments in Alzheimer's disease rat model exposed to chronic mild stress via attenuation of neuroinflamation and inhibition of oxidative stress: Potential role of BDNF

• Published in: Neuroscience and behavioral physiology 2024-10, Vol.54 (8), p.1158-1176
• Main Authors: Bikri, Samir, El Mansouri, Aouatif, Fath, Nada, Benloughmari, Douae, Lamtai, Mouloud, Aboussaleh, Youssef
• Format: Article
• Language: English
• Subjects: Aluminum chloride; Alzheimer's disease; Behavioral Sciences; Biomedical and Life Sciences; Biomedicine; Brain tumors; Brain-derived neurotrophic factor; Corticosterone; D-Galactose; Galactose; Hippocampus; Hydrogen sulfide; Melatonin; Neostriatum; Neurobiology; Neurodegenerative diseases; Neurosciences; Nitric oxide; Oxidative stress; Prefrontal cortex; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 0097-0549; 1573-899X
• DOI: 10.1007/s11055-024-01709-4

Background this study was designed to investigate whether the administration of melatonin and hydrogen-sulfide can ameliorate behavioral and cognitive impairments in a chronically stressed Alzheimer's disease-like rat model induced by aluminum chloride and D-galactose. The research aims to assess the potential of these treatments to alleviate oxidative stress and neuroinflammation, while also reinstating brain-derived neurotrophic factor levels within this rat model. Initially, rats were treated with D-galactose (60 mg/kg) and Aluminium Chloride (100 mg/kg) to induce Alzheimer's disease-like symptoms, followed by four-weeks of exposure to chronic unpredictable mild stress. From the 1st week, melatonin (10 mg/kg/day) and sodium-hydrosulphide (a Hydrogen sulfide donor; 56 μmol/kg/day) treatments were administered for 14 consecutive weeks. Behavioral tests were conducted, and afterward, all rats were anesthetized, and blood was collected for corticosterone analysis. The striatum, prefrontal-cortex, and hippocampus were analyzed for oxidative stress markers, Tumor necrosis factor-alpha, and brain-derived neurotrophic factor levels. Results: findings demonstrated the remarkable effectiveness of melatonin in mitigating cognitive and behavioral impairments induced by Alzheimer's disease combined with chronic unpredictable mild stress in rats, surpassing the effect of hydrogen-sulfide. This distinction arises from melatonin's role in alleviating oxidative stress by restoring superoxide dismutase and catalase levels while simultaneously suppressing Nitric oxide and malondialdehyde production in the striatum, prefrontal-cortex, and hippocampus induced by Alzheimer's disease/chronic unpredictable mild stress. Notably, melatonin treatment also exhibited the capacity to reduce neuroinflammation, as evidenced by restored Tumor necrosis factor-alpha levels in these brain regions. Furthermore, melatonin significantly reinstated brain-derived neurotrophic factor levels in the hippocampus and prefrontal-cortex, in contrast to the effects of hydrogen-sulfide treatment. Conclusion: the findings of this study highlight melatonin's potential as a promising therapeutic strategy for Alzheimer's disease / chronic unpredictable mild stress-related alterations.