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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., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Acute myocardial ischemia provokes sensitization of the adenylyl cyclase system. This sensitization can be differentiated in a receptor-specific and an enzyme-specific sensitization. The receptor-linked sensitization is characterized by an increase of beta-adrenergic receptors in the plasma membranes after 15 mins of global ischemia (49.8 +/- 3.6 to 67 +/- 6 fmol/mg protein) followed by a further increase (89 +/- 4 fmol/mg protein) after 50 min of ischemia in isolated perfused hearts. Concomitantly functionally coupled receptors which are able to bind the beta-agonist with high affinity, increased by 32% after 15 min and by 57% after 50 min of ischemia. The affinities of the receptors for their agonists or their antagonists remain unchanged. Maximally isoproterenol-stimulated adenylyl cyclase activity rose from 66 +/- 7 to 101 +/- 10 pmol cAMP/min/mg protein after 15 min of global ischemia indicating the beta-receptor-specific sensitization of the beta-adrenergic system. This sensitization was followed by a gradual decline of the adenylyl cyclase activity after 30 and 50 min of global ischemia. Additionally, 15 min of myocardial ischemia induced an enzyme-linked sensitization of the adenylyl cyclase activity as indicated by an increase of the forskolin-stimulated activity by about 25% (300 +/- 20 vs 378 +/- 25 pmol cAMP/min/mg protein). In contrast after 50 min of ischemia the total adenylyl cyclase activity declined (232 +/- 24 pmol cAMP/min/mg protein) despite the persistent increase of beta-adrenergic receptors in the plasma membranes. These data demonstrate that the enzyme-specific sensitization is only transient. The early sensitization and late inactivation of the adenylyl cyclase activity occurred independently of receptor activation and could not be prevented by beta-blockade (10(-6) M alprenolol). Cyanide perfusion (1 mM), used to block energy metabolism, lead to energy depletion similar to acute myocardial ischemia. This resulted in an increase of functionally coupled receptors with a time course comparable to that of global ischemia. Additional perfusion with desensitizing concentrations of the beta-agonist isoproterenol did not induce uncoupling or internalization of beta-adrenergic receptors in cyanide treated hearts, suggesting that the rise in functionally coupled receptors is due to a redistribution in part caused by the abolition of continuous receptor internalization. In contrast, the enzyme-linked sensitization is independent of cellular localization of the beta-adrenergic receptors. The increased activity was carried by the enzyme even after partial purification with solubilization and wheat germ affinity chromatography. These data suggest an ischemia-induced, covalent modification of the adenylyl cyclase.(ABSTRACT TRUNCATED AT 400 WORDS)