Alendronate reduces the cognitive and neurological disturbances induced by combined doses of d‐galactose and aluminum chloride in mice

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.

Ginsenoside Rg1 attenuates D‐galactose‐induced neural stem cell senescence via the Sirt1‐Nrf2‐BDNF pathway

“…The biochemical testing on the mice's liver and kidneys did not reveal any appreciable abnormalities. Previous findings (Khedr et al, 2022;Sumbalov a et al, 2022;Zameer et al, 2021;Zeng et al, 2022) were partially supported by the behavioural experiment results, which showed that the older mice were more sad, had worse motor function, and had worsened learning and memory capacities. After receiving Rg1 therapy, this circumstance became better.…”

Naringenin mitigates aluminum toxicity‐induced learning memory impairments and neurodegeneration through amelioration of oxidative stress

“…These free radicals capture the electrons from surrounding biomolecules and create dysfunctions in cellular metabolism. [13] Our results indicate that the treatment of AlCl…”

“…[11] Chronic exposure to aluminum generates free radical and reactive oxygen species (ROS) which interact with lipids and proteins of the cell membrane and cause elevation of LPO, PCO, and AOPP. ROS generation diminishes the activities of antioxidant enzymes (CAT, SOD and GR) and levels of GSH, [12,13] enhances the formation of NO [7] and the activity of acetylcholine esterase (AChE). [13,14] Thus, for the prevention and management of neurodegeneration, inhibition of oxidative stress and AChE targeting mechanisms are the greatest therapeutic strategies.…”

Protective Effect of Ginkgolide B against Cognitive Impairment in Mice via Regulation of Gut Microbiota

“…Cognitive dysfunction is the main expression of AD. d -galactose- and aluminum chloride-induced dementia model, a reliable animal model that resembles human dementia, has been widely used to screen anti-AD agents. , Aluminum chloride could induce neuronal inflammation and Aβ deposition in mice, resulting in learning and memory impairment. , In this study, we used an AD animal model induced with d -galactose and aluminum chloride to explore the effects of GB on AD. Recent studies have indicated that GB could ameliorate the learning and memory ability of vascular dementia rats .…”

“…The animals were randomized into three groups: Con group (control group), AD group (AD model group), and AD + GB group (GB-treated AD). The AD animal model was induced with d -galactose and aluminum chloride, according to previous studies. , Mice in the AD + GB group were intragastrically treated with 0.1% Ginkgolide B (Yuanye Biotechnology Co., Ltd. Shanghai, China) once daily for 2 weeks prior to the induction of AD, then intragastrically treated once daily for 2 weeks after the induction of AD. Mice in the AD and Con groups took the same amount of saline.…”