Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults.

Animal models point towards a key role of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in mediating exercise-induced structural and functional changes in the hippocampus. Recently, also platelet derived growth factor-C (PDGF-C) has been shown to promote blood vessel growth and neuronal survival. Moreover, reductions of these neurotrophic and angiogenic factors in old age have been related to hippocampal atrophy, decreased vascularization and cognitive decline. In a 3-month aerobic exercise study, forty healthy older humans (60 to 77years) were pseudo-randomly assigned to either an aerobic exercise group (indoor treadmill, n=21) or to a control group (indoor progressive-muscle relaxation/stretching, n=19). As reported recently, we found evidence for fitness-related perfusion changes of the aged human hippocampus that were closely linked to changes in episodic memory function. Here, we test whether peripheral levels of BDNF, IGF-I, VEGF or PDGF-C are related to changes in hippocampal blood flow, volume and memory performance. Growth factor levels were not significantly affected by exercise, and their changes were not related to changes in fitness or perfusion. However, changes in IGF-I levels were positively correlated with hippocampal volume changes (derived by manual volumetry and voxel-based morphometry) and late verbal recall performance, a relationship that seemed to be independent of fitness, perfusion or their changes over time. These preliminary findings link IGF-I levels to hippocampal volume changes and putatively hippocampus-dependent memory changes that seem to occur over time independently of exercise. We discuss methodological shortcomings of our study and potential differences in the temporal dynamics of how IGF-1, VEGF and BDNF may be affected by exercise and to what extent these differences may have led to the negative findings reported here.

Insulin-like growth factor-binding protein 4 in children with acute lymphoblastic leukemia.

Insulin-like growth factor-binding protein 4 (IGFBP-4) is a potent inhibitor of IGF-mediated cell proliferation. To investigate the functional relevance of IGFBP-4 in leukemia, we measured plasma IGFBP-4 levels and messenger RNA expression in leukemic cell clones of patients with acute lymphoblastic leukemia (ALL) and in control subjects. The IGFBP-4 levels of ALL patients at diagnosis were significantly lower than the levels of healthy control subjects. We evaluated the patients at diagnosis and after 33 days of chemotherapy and found plasma IGFBP-4 levels at day 33 to be significantly lower than the levels at diagnosis. There was no correlation of plasma IGFBP-4 level with age, sex, immunophenotype, or ALL risk group, and there was no correlation of IGFBP-4 level with plasma IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3 levels. Gene expression analysis of the leukemic blast population at diagnosis revealed that the leukemic clones did not significantly contribute to systemic IGFBP-4 levels. The decrease in plasma IGFBP-4 levels during chemotherapy represents an indirect effect, probably caused by the chemotherapeutic effects on IGFBP-4-expressing cells of the liver and other organs. In addition, IGFBP-4 gene expression was investigated in 13 human immune cell-related cell lines by reverse transcription-polymerase chain reaction analysis. IGFBP-4 was exclusively expressed in cell lines derived either from B-cells or from myelomonocytic cells, whereas IGFBP-4 was not expressed in T-cell lines.