title: Cerebral mTOR signal and pro-inflammatory cytokines in Alzheimer's disease rats.
abstract: As a part of Alzheimer's disease (AD) development the mammalian target of rapamycin (mTOR) has been reported to play a crucial role in regulating cognition and can be used as a neuronal marker. Neuro-inflammation is also a cause of the pathophysiological process in AD. Thus, we examined the protein expression levels of mTOR and its downstream pathways as well as pro-inflammatory cytokines (PICs) in the brain of AD rats. We further examined the effects of blocking mTOR on PICs, namely IL-1β, IL-6 and TNF-α. Our results showed that the protein expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) pathways were amplified in the hippocampus of AD rats compared with controls. Blocking mTOR by using rapamycin selectively enhanced activities of IL-6 and TNF-α signaling pathways, which was accompanied with an increase of Caspase-3, indicating cellular apoptosis and worsened learning performance. In conclusion, our data for the first time revealed specific signaling pathways engaged in the development of AD, including a regulatory role by the activation of mTOR in PIC mechanisms. Stimulation of mTOR is likely to play a beneficial role in modulating neurological deficits in AD.Targeting one or more of these signaling molecules may present with new opportunities for treatment and clinical management of AD.
authors.affiliation: Department of Neurology and Neuroscience Center, The First Hospital of Jilin University Changchun, Jilin 130021, PR. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology and Neuroscience Center, The First Hospital of Jilin University Changchun, Jilin 130021, PR. China.
authors.forename: Guang-Jian
authors.initials: GJ
authors.lastname: Li
authors.affiliation: Department of Emergency Medicine, The First Hospital of Jilin University Changchun, Jilin 130021, PR. China.
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Hu
authors.affiliation: Department of Brain Tumor Surgery, The First Hospital of Jilin University Changchun, Jilin 130021, P.R. China.
authors.forename: Chi
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Neurology and Neuroscience Center, The First Hospital of Jilin University Changchun, Jilin 130021, PR. China.
authors.forename: Di-Hui
authors.initials: DH
authors.lastname: Ma
authors.affiliation: Department of Emergency Medicine, The First Hospital of Jilin University Changchun, Jilin 130021, PR. China.
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Liu
authors.affiliation: Department of Emergency Medicine, The First Hospital of Jilin University Changchun, Jilin 130021, PR. China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Jiang
keywords: Alzheimer’s disease; Caspase-3; Hippocampus; Mammalian target of rapamycin (mTOR); Pro-inflammatory cytokines