Effects and mechanism of amyloid β1-42 on mitochondria in astrocytes

Abstract

Amyloid β (Aβ)1–42 is strongly associated with Alzheimer's disease (AD). The effects of Aβ1–42 on astrocytes remain largely unknown. The present study focused on the effects of Aβ1–42 on U87 human glioblastoma cells as astrocytes for in vitro investigation and mouse brains for in vivo investigation. The mechanism and regulation of mitochondria and cytochrome P450 reductase (CPR) were also investigated. As determined by MTT assays, low doses of Aβ1–42 (<1 µM) marginally promoted astrocytosis compared with the 0 µM group within 24 h, however, after 48 h treatment these doses reduced cellular growth compared with the 0 µM group. Furthermore, Aβ1–42 doses >5 µM inhibited the growth of U87 cells compared with the 0 µM group after 24 and 48 h treatment. Immunofluorescence analysis demonstrated that astrocytosis was also observed in early stage AD mice compared with wild-type (WT) mice. In addition, concentrations of Aβ1–42 were also significantly higher in early stage AD mice compared with WT mice, however, the levels were markedly lower compared with later stage AD mice, as determined by ELISA. In addition to increased levels of Aβ1–42 in mice with later stage AD, reduced astrocyte staining was observed compared with WT mice. Western blotting indicated that the effect of Aβ1–42 on U87 cell apoptosis may be regulated via Bcl-2 and caspase-3 located in mitochondria, whose functions, including adenosine triphosphate generation, electron transport chain and mitochondrial membrane potential, were inhibited by Aβ1–42. During this process, the expression and activity of cytochrome P450 reductase was also downregulated. The current study provides novel insight into the effects of Aβ1–42 on astrocytes and highlights a potential role for astrocytes in the protection against AD.

2-Bromopalmitate attenuates bone cancer pain via reversing mitochondrial fusion and fission imbalance in spinal astrocytes

“…5,6 In CNS, astrocytes are structurally in close association with synapses, contributing to the establishment and reorganization of neuronal circuits and maintenance of synaptic structure. 7 In addition to physiological functions, astrocytes contribute to chronic pain. Research demonstrates that in chronic pain and pain-related injury states, activation of astrocytes usually occurring several days after the injury and much longer lasting.…”

Altered Brain Leptin and Leptin Receptor Expression in the 5XFAD Mouse Model of Alzheimer’s Disease

“…There was also no difference (t(10) = 9.993, p < 0.081, Cohen's D = 1.21) in neuronal LepR expression ( Figure 2e) between young-WT (M = 8103.67, SD = 1659.65) and young-Tg (M = 6266.98, SD = 1615.97) mice. Although our data presents a marginal reduction in leptin and LepR expression between the WT and 5XFAD mice, there was no significant difference in leptin expression ( Figure 2d (48)(49)(50)(51)(52) week) 5XFAD (Tg) mice and wild-type (WT) controls. Independent t-test analysis of (a) neuronal leptin and (e) LepR expression between the young-WT and young-Tg revealed no significant differences.…”

“…We too observed leptin and LepR expression in activated astrocytes in both young and old Tg mice. We propose that astrocytic expression of these proteins reflect the nutritional demands placed upon glial cells during all phases of AD development, whereby they clear Aβ and consequent plaques formed in the brain [ 51 , 52 ]. In support, we observed GFAP-positive astrocytes surrounding amyloid plaques in both young- and old-Tg mice ( Figure 4 and Figure 5 ).…”

Antioxidant activities of inula viscosa extract and curcumin on U87 cells induced by beta-amyloid

“…The cell line was replicated in flasks using this medium. The U87 cell line density in the flask, which was kept in the incubator for 48 hours, was examined under a light microscope and the cells were passage from the intense flasks 19 .…”