Are there differences between the secretion characteristics of NGF and BDNF? Implications for the modulatory role of neurotrophins in activity-dependent neuronal plasticity

In previous experiments the activity-dependent secretion of nerve growth fa ctor (NGF) from native hippocampal slices and from NGF-cDNA transfected hip pocampal neurons showed unusual characteristics [Blochl and Thoenen (1995) fur J Neurosci 7:1220-1228; (1996) Mol Cell Neurosci 7:173-190]. In both hi ppocampal slices and cultured hippocampal neurons the activity-dependent se cretion proved to be independent of extracellular calcium, but dependent on the release of calcium from intracellular stores. Under different experime ntal conditions, Goodman et al. [(1996) Mol Cell Neurosci 7:222-238] report ed that the high potassium-mediated secretion of brain-derived neurotrophic factor (BDNF) from hippocampal cultures was dependent on extracellular cal cium. Mowla et al. [(1997) Proc 27th Annu Meet Soc Neurosci New Orleans 875 .10] reported on even further-reaching differences between NGF and BDNF sec retion, namely, that in hippocampal neurons and in pituitary cell lines NGF was secreted exclusively according to the constitutive pathway, whereas BD NF was exclusively sorted according to the activity-dependent regulated pat hway. In view of the crucial importance of such potential differences betwe en the processing, sorting, and secretory mechanisms of different neurotrop hins for their modulatory roles in activity-dependent neuronal plasticity, a thorough analysis under comparable experimental conditions was mandatory. We demonstrate that in native hippocampal slices and adenoviral-transduced hippocampal neurons there are no differences between NGF and BDNF with res pect to the subcellular distribution and mechanism of secretion; that the a ctivity-dependent secretion of both NGF and BDNF is dependent on intact int racellular calcium stores; and that the differences between our own observa tions and these of Goodman et al. (ibid.) regarding the dependence on extra cellular calcium do not reflect differences between NGF and BDNF sorting an d secretion, but reflect the differing experimental conditions used. Micros c. Res. Tech. 45:262-275, 1999. (C) 1999 Wiley-Liss, Inc.