title: Acceleration of TDP43 and FUS/TLS protein expressions in the preconditioned hippocampus following repeated transient ischemia.
abstract: The 43-kDa transactivation response DNA binding protein (TDP43), fused in sarcoma/translocated in liposarcoma (FUS/TLS), heat shock protein 70 (HSP70), and β-amyloid (Aβ) are induced and involved in cerebral ischemia, amyotrophic lateral sclerosis (ALS), and Alzheimer's disease (AD), but their relationships in ischemic tolerance have never been examined, although they could be involved in endogenous neuroprotection under ischemic preconditioning. In the present study, Mongolian gerbils were subjected to one or three incidents of basically nonlethal 2-min transient common carotid arteries occlusion (tCCAO). Hippocampal CA1 neurons were lost only in the 2-min three times group at 3 and 7 days, which then gradually recovered from 1 to 6 months. Inductions of TDP43 and FUS/TLS were accelerated from 3 months to 7 days or from 7 days to 1 day, respectively, after 2-min three times ischemia compared with once. The cytoplasmic stainings of TDP43 and FUS/TLS showed a further acceleration of the peaks from 1 months to 3 days or from 1 months to 7 days, respectively, after 2-min three times ischemia compared with once. In contrast, HSP70 was induced only at 7 days after 2-min tCCAO for three times, with no expression for Aβ. These data show that ischemic preconditioning offers a way to induce endogenous neuroprotection and neurogenesis in gerbils, with TDP43, FUS/TLS, and HSP70 involved in this function.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan; Department of Neurology, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.forename: Toru
authors.initials: T
authors.lastname: Yamashita
authors.forename: Jingwei
authors.initials: J
authors.lastname: Shang
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Kentaro
authors.initials: K
authors.lastname: Deguchi
authors.forename: Wentao
authors.initials: W
authors.lastname: Liu
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Juan
authors.initials: J
authors.lastname: Feng
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005849:Gerbillinae; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D019194:Ischemic Preconditioning; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D034702:RNA-Binding Protein FUS / Q000378:metabolism*; D013997:Time Factors
chemical_list: D004268:DNA-Binding Proteins; D050884:HSP72 Heat-Shock Proteins; D034702:RNA-Binding Protein FUS
keywords: FUS/TLS; HSP70; TDP43; ischemic preconditioning; neuroprotection