Alendronate reduces the cognitive and neurological disturbances induced by combined doses of d‐galactose and aluminum chloride in mice. Issue 11 (10th March 2021)

• Record Type: Journal Article
• Authors: Zameer, Saima; Hussain, Salman; Vohora, Divya; Kalam Najmi, Abul; Ali, Javed; Akhtar, Mohd
• Is Part Of: Journal of applied toxicology. Volume 41:Issue 11(2021)
• Page Start: 1779
• Page End: 1793
• Publication Date: 2021-03-10
• Subjects: alendronate -- aluminum trichloride -- Alzheimer's disease -- amyloid‐beta -- d‐galactose -- GSK‐3β; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.4160
• Languages: English
• ISSNs: 0260-437X

Abstract

Abstract: Neurological disturbances including cholinergic dysfunction, oxidative stress, neuroinflammation, and cognitive impairments are the well‐reported consequences of old age‐related disorders like Alzheimer's disease (AD) or dementia. Bisphosphonates were shown to ameliorate dementia in osteoporotic patients, neuroinflammation, and cholinesterase activity in rodents. Thus, the present study has been designed to examine the role of alendronate against cognitive and neurological disturbances in mice induced by a combined oral dose of d ‐galactose and aluminum chloride (AlCl3 ) for 6 weeks. d ‐galactose acts as a senescence agent, whereas AlCl3 is a neurotoxin and in combination generates neuropathologies and cognitive depletion resembling aging and AD. It was found that memory was markedly impaired in d ‐galactose + AlCl3 ‐treated mice as assessed in different behavioral paradigms. Additionally, d ‐galactose + AlCl3 led to neurotoxicity assessed on the basis of neuroinflammation, oxidative stress, glial cell activation, neuronal damage, and augmented GSK‐3β level in mice hippocampus. Consequently, alendronate administration orally for 15 days in d ‐galactose + AlCl3 ‐exposed mice prominently reversed all these behavioral and neuropathological changes. These findings show that alendronate can be a potential therapeutic molecule with multiple targets for the management of age‐related neurological disorders such as AD. Abstract : Aluminium trichloride (AlCl3) and D‐galactose act as neurotoxins and induce neuropathological changes and cognitive impairments similar to Sporadic Alzheimer's disease (SAD) and aging SAD is a most prevalent and complex neurodegenerative disease manifested by cognitive decline, senile plaques and neurofibrillary tangles. Oral dose of alendronate for 15 days attenuates AlCl3+D‐galactosed induced augmented amyloid precursor protein (APP) processing, Aβ production, GSK‐3β and associated neuroinflammation. Alendronate also found to reduce neurodegeneration and Aβ deposition in CA1 and CA3 region of mice hippocampus.