Insulin-like growth factor-1 selectively increases glucose utilization in brains of aged animals

Previous studies indicate that insulin-like growth factor-1 is an important neurotrophic agent and that decreases in brain concentrations of IGF-1 and the type 1 IGF receptor have an important role in the age-related decline in memory. neuronal function and possibly dendritic architecture. In this s tudy, we assessed the effects of age and IGF-1 replacement on local cerebra l glucose utilization (LCGU). Three groups of male Brown-Norway rats (7, 18 and 28 months of age) were implanted with Alzet minipumps and either salin e or IGF-1 (50ng/0.5 mul/hour)was infused into the lateral ventricle for 28 days. On day 28, LCGU was measured by infusion of 2-[C-14]deoxyglucose dur ing the dark phase of the light/dark cycle. Results indicate that glucose u tilization significantly decreased with age throughout the brain including the anterior cingulate, sensorimotor and retrosplenial cortex, CA1, CA3 and dentate gyrus of hippocampus and several regions of the hypothalamus. Admi nistration of IGF-1 to aged animals increased rates of LCGU in the anterior cingulate of the cortex (14.2%), CA 1 region of the hippocampus (11.0%) an d the arcuate nucleus of the hypothalamus (12.0%). Our results indicate tha t although glucose utilization decreases with age throughout the brain, the effects of IGF-1 infusion are manifest only in specific brain regions. Sin ce IGF-1 has been shown to reverse the age-related decrease in memory, thes e results suggest that despite the wide distribution of the type 1 IGF rece ptor the actions of IGF-1 on glucose utilization are highly localized. Addi tionally, the close association between glucose utilization and excitatory amino acid activity suggests that IGF-1 may act on specific neural pathways to increase glutamate activity in brain regions associated with learning a nd memory.