BACKGROUND: @entity1 studies suggest @entity286 smoking is a risk factor for @entity73 and @entity179 , including @entity195 ( @entity195 ). However, experimental data linking @entity286 smoke exposures to underlying mediators of @entity179 , including @entity851 factor (IGF) signaling in @entity195 are lacking. OBJECTIVE: This study tests the hypothesis that cigarette smoke (CS) exposures can impair brain insulin/IGF signaling and alter expression of @entity195 -associated proteins. METHODS: Adult male A/J @entity19 were exposed to air for 8 weeks (A8), CS for 4 or 8 weeks (CS4, CS8), or CS8 followed by 2 weeks recovery (CS8+R). Gene expression was measured by qRT-PCR analysis and proteins were measured by multiplex bead-based or direct binding duplex ELISAs. RESULTS: CS exposure effects on insulin/IGF and insulin receptor substrate (IRS) proteins and phosphorylated proteins were striking compared with the mRNA. The main consequences of CS4 or CS8 exposures were to significantly reduce insulin R, IGF-1R, IRS-1, and @entity4149 phosphorylated insulin R and IGF-1R proteins. Paradoxically, these effects were even greater in the CS8+R group. In addition, relative levels of S312-IRS-1, which inhibits downstream signaling, were increased in the CS4, CS8, and CS8+R groups. Correspondingly, CS and CS8+R exposures inhibited expression of proteins and phosphoproteins required for signaling through Akt, PRAS40, and/or p70S6K, increased AbPP-Ab, and reduced ASPH protein, which is a target of insulin/IGF-1 signaling. CONCLUSION: Secondhand CS exposures caused molecular and biochemical abnormalities in brain that overlap with the findings in @entity195 , and many of these effects were sustained or worsened despite short-term CS withdrawal.

XXXX Smoke Exposure Impairs Brain Insulin/IGF Signaling: Potential Co-Factor Role in Neurodegeneration.

@entity1 :: ('9606', 'Species') :: ['Human'] @entity286 :: ('4097', 'Species') :: ['tobacco'] @entity851 :: ('MESH:D006130', 'Disease') :: ['impairments in brain insulin and insulin-like growth'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity73 :: ('MESH:D003072', 'Disease') :: ['cognitive impairment'] @entity179 :: ('MESH:D019636', 'Disease') :: ['neurodegeneration'] @entity195 :: ('MESH:D000544', 'Disease') :: ['AD', "Alzheimer's disease"] @entity4149 :: ('D014443', 'Chemical') :: ['tyrosine']
@entity286 :: (4097,Species) :: ['Tobacco']
