Age-related changes in levels of tyrosine kinase B receptor and fibroblastgrowth factor receptor 2 in the rat inferior colliculus: Implications for neural senescence

Brain-derived neurotrophic factor and fibroblast growth factor 2, and their respective binding sites, tyrosine kinase B receptor and fibroblast growth factor receptor 2, are known to regulate neurite outgrowth and antioxidant enzyme activity. Several studies suggest that brain-derived neurotrophic f actor and fibroblast growth factor are contained in the inferior colliculus . Previous work in our laboratories revealed dendritic and synaptic losses in the inferior colliculus of aged Fischer-344 rats, along with coincident increases in lipid peroxidation possibly linked to a decrease in activity o f antioxidant enzymes. In an effort to identify potential causal mechanisms underlying age-related synaptic and dendritic losses that occur in the inf erior colliculus, the present study attempted to determine if inferior coll iculus levels of tyrosine kinase B receptor and fibroblast growth factor re ceptor 2 expression are altered with age. Immunocytochemistry was performed in the inferior colliculus, hippocampus a nd cerebellum of 3-month-old F344 rats to study distributions of the full-l ength and truncated isoforms of tyrosine kinase B receptor, and fibroblast growth factor receptor 2. The latter two brain regions served as positive c ontrols. For all three antigens, immunolabeling was localized primarily in somata and proximal dendrites in all subdivisions of the inferior colliculu s, and in the dentate gyrus and Ammon's horn of the hippocampus. In the cer ebellum, the somata and dendrites of the Purkinje cells were also immunolab eled. A significant reduction in levels of the full-length form of tyrosine kinas e B receptor in 18- and 25-month-old rats (respectively, similar to 20% and 30% relative to 3-month-olds) was revealed using western blot analyses. In ferior colliculus and hippocampal levels of the truncated form were modestl y decreased (similar to7%) as well in the two older age groups. In contrast , levels of fibroblast growth factor receptor 2 in the inferior colliculus and hippocampus were elevated by approximately 35% in the two older age gro ups when compared to 3-month-olds. Changes in cerebellar levels of tyrosine kinase B receptor and fibroblast growth factor receptor 2, while similar t o those in the inferior colliculus and hippocampus among the age groups, di d not achieve statistical significance in this study. These findings give rise to the possibility that age-related reductions in tyrosine kinase B receptor levels could be a causal factor in the degenerat ive changes observed in the inferior colliculus of aged animals, including mitochondrial damage and dendritic regression. The observed increases in fi broblast growth factor receptor 2 levels may be compensatory to the increas ed oxidative stress. The effectiveness of the fibroblast growth factor rece ptor 2 response is questionable given the damage that occurs in the inferio r colliculus and hippocampus of aged animals. However, the deficits could w orsen in the absence of an increase in fibroblast growth factor receptor 2. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.