Browsing by Author "Sonntag, W."

Filter results by typing the first few letters
Now showing 1 - 2 of 2
  • Thumbnail Image
    ItemOpen Access
    Spatial learning and memory deficits after whole-brain irradiation are associated with changes in nmda receptor subunits in the hippocampus
    (Radiation Research Society., 2006) Shi, L.; Adams, Michelle M.; Long, A.; Carter, C.; Bennett, C.; Sonntag, W.; Nicolle, M.; Robbins, M.; D'Agostino, R.; Brunso-Bechtold, J.
    Whole-brain irradiation is used for the treatment of brain tumors, but can it also induce neural changes, with progressive dementia occurring in 20–50% of long-term survivors. The present study investigated whether 45 Gy of whole-brain irradiation delivered to 12-month-old Fischer 344 × Brown Norway rats as nine fractions over 4.5 weeks leads to impaired Morris water maze (MWM) performance 12 months later. Compared to sham-irradiated rats, the irradiated rats demonstrated impaired MWM performance. The relative levels of the NR1 and NR2A but not the NR2B subunits of the NMDA receptor were significantly higher in hippocampal CA1 of irradiated rats compared to control rats. No significant differences were detected for these NMDA subunits in CA3 or dentate gyrus. Further analysis of CA1 revealed that the relative levels of the GluR1 and GluR2 subunits of the AMPA receptor and synaptophysin were not altered by whole-brain irradiation. In summary, a clinically relevant regimen of fractionated whole-brain irradiation led to significant impairments in spatial learning and reference memory and alterations in the relative levels of subunits of the NMDA, but not the AMPA, receptors in hippocampal CA1. These findings suggest for the first time that radiation-induced cognitive impairments may be associated with alterations in glutamate receptor composition.
  • Thumbnail Image
    ItemOpen Access
    Stability of local brain levels of insulin-like growth factor-I in two well-characterized models of decreased plasma IGF-I
    (Taylor & Francis, 2009) Adams, Michelle M.; Forbes, M; Linville, M.; Riddle, D.; Sonntag, W.; Brunso-Bechtold, J.
    Insulin-like growth factor-I (IGF-I), a functionally important neurotrophic factor, impacts tissues throughout the body including the central nervous system. In addition to the significant proportion of IGF-I that is synthesized in the liver and released into the plasma, IGF-I is expressed locally in tissues. The present study investigated the relationship between plasma and local brain levels of IGF-I in two well-characterized models of decreased IGF-I. The first is an adult-onset growth hormone deficiency (AOGHD) model, and the second is a caloric restriction (CR) model. In the first cohort of animals from both models, the hippocampus was removed from the brain immediately following decapitation, and in the second cohort, the animals were perfused transcardially with phosphate buffered saline to remove cerebral blood prior to harvesting the hippocampus. Our results demonstrated that although the plasma IGF-I levels were decreased in the CR and AOGHD rats compared to controls, the hippocampal IGF-I levels did not differ among the groups. These data suggest that local brain IGF-I levels are regulated in a different manner than plasma IGF-I levels.