Biotin, coenzyme Q10, and their combination ameliorate aluminium chloride‐induced Alzheimer's disease via attenuating neuroinflammation and improving brain insulin signaling

Abstract

Insulin is important for brain function and neuronal survival. Insulin signaling is initiated by the phosphorylation of insulin receptor substrate‐1 (IRS‐1) at tyrosine (pTyr) residue. However, IRS‐1 is inhibited by phosphorylation at serine (pSer). In Alzheimer's disease (AD), oxidative stress and accumulation of amyloid beta (Aβ) induce neuroinflammation, which augments pSer‐IRS‐1 and reduces pTyr‐IRS‐1 disturbing insulin signaling pathway. Coenzyme Q10 (CoQ10) and biotin possess antioxidant and anti‐inflammatory properties, and, in this study, their impact on insulin signaling is investigated in an aluminium chloride (AlCl3) model of AD. AD was induced by oral administration of AlCl3 (75 mg/kg) for 60 days. Biotin (2 mg/kg), CoQ10 (10 mg/kg), and their combination were supplemented concomitantly with AlCl3 for 60 days. Memory test and histological examination were performed. Brain levels of lipid peroxides, antioxidants (reduced glutathione and superoxide dismutase), inflammatory markers (tumor necrosis factor‐α, interleukin‐6 [IL‐6], IL‐1, and nuclear factor κB), and phosphorylated Akt (survival kinase) as well as protein levels of Aβ, IRS‐1 (pTyr and pSer), and caspase‐3 (apoptotic marker) were determined. AlCl3 resulted in impaired memory, significant increase in Aβ, lipid peroxides, inflammatory markers, caspase‐3, and pSer‐IRS‐1, with significant reduction of the antioxidants, pTyr‐IRS‐1, and p‐Akt reflecting Aβ‐induced inflammation and defective insulin signaling. Histological examination revealed focal aggregations of inflammatory cells and neuronal degeneration. The biochemical deviations and histological changes were attenuated by the concomitant treatment with biotin and, to greater extent, with CoQ10 and the combination. In conclusion, biotin and CoQ10 could protect against AD via attenuating inflammatory response and enhancing insulin signaling.

Celecoxib effect on rivastigmine anti-Alzheimer activity against aluminum chloride-induced neurobehavioral deficits as a rat model of Alzheimer's disease; novel perspectives for an old drug

“…Al is thought to cause cell death by triggering apoptotic pathways mediated by stress processes in the mitochondria or endoplasmic reticulum [220]. In Al-intoxicated rats, the protein level of activated caspase-3 was significantly increased relative to the Cont group, consistent with other studies [137,[221][222][223][224][225][226]. The RIVA group displayed a significant reduction of the activated caspase-3 expression compared to the AL group, consistent with other research findings [227,228].…”

Changes in the Immunity, Histopathology, and Metabolism of Crayfish (Procambarus clarkii) in Response to Drought

“…Therefore, lymphocytes may be sensitive to the biotin status. In addition, biotin deficiency increases the expression of proinflammatory cytokine genes, such as interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and interferon γ2 (IFN-γ2), and enhances the inflammatory response [ 58 , 59 , 60 , 61 ]. The decrease in biotin in crayfish after drought exposure may be further supporting evidence for reduced immune function and increased inflammatory hepatopancreas injury.…”

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

“…A clinical trial showed that the level of neurodegeneration in AD patients was significantly increased with neurological dysfunction . In addition, neurofibrillary degeneration and focal aggregation of degenerated neurons could be presented in aluminum chloride-induced mice. , Recent studies showed that GB was able to alleviate the hippocampal neuron injury and neurological dysfunction induced by hypoxia in rats . In this study, GB could improve the pathological change in AD mice.…”