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Property "Has-20abstract" (as page type) with input value "A-20decline-20in-20mitochondrial-20function-20and-20biogenesis-20as-20well-20as-20increased-20reactive-20oxygen-20species-20(ROS)-20are-20important-20determinants-20of-20aging.-20With-20advancing-20age,-20there-20is-20a-20concomitant-20reduction-20in-20circulating-20levels-20of-20insulin-2Dlike-20growth-20factor-2D1-20(IGF-2D1)-20that-20is-20closely-20associated-20with-20neuronal-20aging-20and-20neurodegeneration.-20In-20this-20study,-20we-20investigated-20the-20effect-20of-20the-20decline-20in-20IGF-2D1-20signaling-20with-20age-20on-20astrocyte-20mitochondrial-20metabolism-20and-20astrocyte-20function-20and-20its-20association-20with-20learning-20and-20memory.-0A-0ALearning-20and-20memory-20was-20assessed-20using-20the-20radial-20arm-20water-20maze-20in-20young-20and-20old-20mice-20as-20well-20as-20tamoxifen-2Dinducible-20astrocyte-2Dspecific-20knockout-20of-20IGFR-20(GFAP-2DCre-3Csup-3ETAM-3C-2Fsup-3E-2Figfr-3Csup-3Ef-2Ff-3C-2Fsup-3E).-20The-20impact-20of-20IGF-2D1-20signaling-20on-20mitochondrial-20function-20was-20evaluated-20using-20primary-20astrocyte-20cultures-20from-20igfr-3Csup-3Ef-2Ff-3C-2Fsup-3E-20mice-20using-20AAV-2DCre-20mediated-20knockdown-20using-20Oroboros-20respirometry-20and-20Seahorse-20assays.-0A-0AOur-20results-20indicate-20that-20a-20reduction-20in-20IGF-2D1-20receptor-20(IGFR)-20expression-20with-20age-20is-20associated-20with-20decline-20in-20hippocampal-2Ddependent-20learning-20and-20increased-20gliosis.-20Astrocyte-2Dspecific-20knockout-20of-20IGFR-20also-20induced-20impairments-20in-20working-20memory.-20Using-20primary-20astrocyte-20cultures,-20we-20show-20that-20reducing-20IGF-2D1-20signaling-20via-20a-2030-2D50-25-20reduction-20IGFR-20expression,-20comparable-20to-20the-20physiological-20changes-20in-20IGF-2D1-20that-20occur-20with-20age,-20significantly-20impaired-20ATP-20synthesis.-20IGFR-20deficient-20astrocytes-20also-20displayed-20altered-20mitochondrial-20structure-20and-20function-20and-20increased-20mitochondrial-20ROS-20production-20associated-20with-20the-20induction-20of-20an-20antioxidant-20response.-20However,-20IGFR-20deficient-20astrocytes-20were-20more-20sensitive-20to-20H-3Csub-3E2-3C-2Fsub-3EO-3Csub-3E2-3C-2Fsub-3E-2Dinduced-20cytotoxicity.-20Moreover,-20IGFR-20deficient-20astrocytes-20also-20showed-20significantly-20impaired-20glucose-20and-20Aβ-20uptake,-20both-20critical-20functions-20of-20astrocytes-20in-20the-20brain.-0A-0ARegulation-20of-20astrocytic-20mitochondrial-20function-20and-20redox-20status-20by-20IGF-2D1-20is-20essential-20to-20maintain-20astrocytic-20function-20and-20coordinate-20hippocampal-2Ddependent-20spatial-20learning.-20Age-2Drelated-20astrocytic-20dysfunction-20caused-20by-20diminished-20IGF-2D1-20signaling-20may-20contribute-20to-20the-20pathogenesis-20of-20Alzheimer's-20disease-20and-20other-20age-2Dassociated-20cognitive-20pathologies.-0A-0ACopyright-20©-202018-20The-20Authors.-20Published-20by-20Elsevier-20GmbH.-20All-20rights-20reserved." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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