Contrasting effects of chronic, systemic treatment with mTOR inhibitors rapamycin and metformin on adult neural progenitors in mice
Kusne Y, Goldberg EL, Parker SS, Hapak SM, Maskaykina IY, Chew WM, Limesand KH, Brooks HL, Price TJ, Sanai N, Nikolich-Zugich J, Ghosh S. Contrasting effects of chronic, systemic treatment with mTOR inhibitors rapamycin and metformin on adult neural progenitors in mice. GeroScience 2013, 36: 199-212. PMID: 23949159, PMCID: PMC3889877, DOI: 10.1007/s11357-013-9572-5.Peer-Reviewed Original ResearchConceptsSystemic administrationMTOR inhibitorsImproved health spanAdult-born neuronsHealth spanEffects of chronicNeural progenitorsAdult neural stem cellsMTOR inhibitor rapamycinInhibition of mTORPotential adverse effectsAdult neural progenitorsNeural stem cellsSystemic treatmentDendate gyrusMouse hippocampusSubventricular regionOrgan functionMetforminBehavioral healthInhibitor rapamycinAdverse effectsPharmacological inhibitorsMTORRapamycinmTORC1 inhibition induces pain via IRS-1-dependent feedback activation of ERK
Melemedjian OK, Khoutorsky A, Sorge RE, Yan J, Asiedu MN, Valdez A, Ghosh S, Dussor G, Mogil JS, Sonenberg N, Price TJ. mTORC1 inhibition induces pain via IRS-1-dependent feedback activation of ERK. Pain 2013, 154: 1080-1091. PMID: 23607966, PMCID: PMC3742001, DOI: 10.1016/j.pain.2013.03.021.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDown-RegulationEnzyme ActivationFeedback, PhysiologicalInsulin Receptor Substrate ProteinsMaleMAP Kinase Signaling SystemMechanistic Target of Rapamycin Complex 1MiceMice, Inbred C57BLMice, Inbred ICRMultiprotein ComplexesPainRatsRats, Sprague-DawleySensory Receptor CellsSirolimusTOR Serine-Threonine KinasesConceptsSpontaneous painMechanical hypersensitivitySensory neuronsDevelopment of painPotential treatment optionSensory neuron sensitizationRapamycin complex 1 (mTORC1) inhibitorsExtracellular signal-regulated kinase (ERK) pathwaySignal-regulated kinase pathwaySuppression of S6K1Chronic treatmentPain conditionsPain therapeuticsTransplant rejectionAdenosine monophosphate-activated protein kinase (AMPK) activatorProtein kinase activatorsTreatment optionsAntidiabetic drugsPainSensory hypersensitivityMTOR pathwayNegative feedback loopCertain cancersMammalian targetMTORC1 inhibition