The control of [125I]BDNF release from striatal rat brain slices

The depolarisation-induced release of brain-derived neurotrophic factor (BDNF) from adult rat striatal slices was studied in vitro. The slices were preloaded with [I-125]BDNF and exposed to depolarising stimulation with varying concentrations of veratrine (up to 50 muM) and potassium (up to 50 mM) which caused activity-dependent short-term release of [I-125]BDNF. The results indicate that this stimulated release of [I-125]BDNF is not regulated by a feedback mechanism mediated via the TrkB receptor. The release of [I-125]BDNF was found to be dependent on the concentrations of both extracellular and intracellular calcium, since BDNF release was modulated by the addition of both EGTA and BAPTA-AM, agents chelating either external or internal Ca2+, respectively. BDNF release also proved to be dependent on activation of IP3 mediated Ca2+ release from intracellular stores. [I-125]BDNF release was also modulated by 5HT(3) receptor ligands and by receptors coupled to adenylate cyclase. Taken together, these results indicate that [I-125]BDNF release is activity dependent, and is modulated by changes in Ca2+ levels. Moreover the release occurs via a mechanism involving cAMP. (C) 2003 Elsevier Science B.V. All rights reserved.