Intranasal insulin activates Akt2 signaling pathway in the hippocampus of wild-type but not in APP/PS1 Alzheimer model mice.

Autor: Gabbouj S; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland., Natunen T; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland., Koivisto H; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland., Jokivarsi K; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland., Takalo M; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland., Marttinen M; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland., Wittrahm R; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland., Kemppainen S; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland., Naderi R; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland; Department of Biology, Shahid Bahonar University, Kerman, Iran., Posado-Fernández A; STAB VIDA Lda, Madan Parque, Rua dos Inventores, Caparica, Portugal., Ryhänen S; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland., Mäkinen P; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland., Paldanius KMA; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland., Doria G; STAB VIDA Lda, Madan Parque, Rua dos Inventores, Caparica, Portugal., Poutiainen P; Diagnostic Imaging Centre, PET Radiopharmacy, Kuopio University Hospital, Kuopio, Finland., Flores O; STAB VIDA Lda, Madan Parque, Rua dos Inventores, Caparica, Portugal., Haapasalo A; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland., Tanila H; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland., Hiltunen M; Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland. Electronic address: mikko.hiltunen@uef.fi.
Jazyk: angličtina
Zdroj: Neurobiology of aging [Neurobiol Aging] 2019 Mar; Vol. 75, pp. 98-108. Date of Electronic Publication: 2018 Nov 17.
DOI: 10.1016/j.neurobiolaging.2018.11.008
Abstrakt: Type 2 diabetes mellitus (T2DM) increases the risk for Alzheimer's disease (AD). Human AD brains show reduced glucose metabolism as measured by [18F]fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG-PET). Here, we used 14-month-old wild-type (WT) and APP Swe /PS1 dE9 (APP/PS1) transgenic mice to investigate how a single dose of intranasal insulin modulates brain glucose metabolism using FDG-PET and affects spatial learning and memory. We also assessed how insulin influences the activity of Akt1 and Akt2 kinases, the expression of glial and neuronal markers, and autophagy in the hippocampus. Intranasal insulin moderately increased glucose metabolism and specifically activated Akt2 and its downstream signaling in the hippocampus of WT, but not APP/PS1 mice. Furthermore, insulin differentially affected the expression of homeostatic microglia markers P2ry12 and Cx3cr1 and autophagy in the hippocampus of WT and APP/PS1 mice. We found no evidence that a single dose of intranasal insulin improves overnight memory. Our results suggest that intranasal insulin exerts diverse effects on Akt2 signaling, autophagy, and the homeostatic status of microglia depending on the degree of AD-related pathology.
(Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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