BDNF, an important nerve growth factor that is expressed at high levels in the brain, is best known for its role, in rodent models, in promoting the functioning of the adult hippocampus, including the survival of newly born granule cell neurons throughout adult life. In rodents, stress decreases BDNF expression in the hippocampus, an effect that is reversed by chronic antidepressant treatment38. Similar findings have been observed in human hippocampus examined post-mortem. However, BDNF exerts very different effects in other brain regions. Chronic stress increases BDNF expression in the rodent nucleus accumbens, and this has been linked to prodepression-like effects in several behavioural assays39,40. Interestingly, this induction of BDNF is causally related to the degree to which rodents are vulnerable versus resilient to the deleterious effects of stress (for example, passive coping, social avoidance and anhedonia), with resilient individuals showing no increase in BDNF levels41. Humans with depression also show increased BDNF levels in the nucleus accumbens41, which highlights the very different effects exerted by BDNF in different neural circuits. Indeed, stress also produces distinct effects on BDNF in the amygdala and the PFC, but BDNF in these regions has not yet been studied in resilience models.
