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 [125I]BDNF and exposed to depolarising stimulation with varying concentrations of veratrine (up to 50 microM) and potassium (up to 50 mM) which caused activity-dependent short-term release of [125I]BDNF. The results indicate that this stimulated release of [125I]BDNF is not regulated by a feedback mechanism mediated via the TrkB receptor. The release of [125I]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 Ca(2+), respectively. BDNF release also proved to be dependent on activation of IP(3) mediated Ca(2+) release from intracellular stores. [125I]BDNF release was also modulated by 5HT(3) receptor ligands and by receptors coupled to adenylate cyclase. Taken together, these results indicate that [125I]BDNF release is activity dependent, and is modulated by changes in Ca(2+) levels. Moreover the release occurs via a mechanism involving cAMP.