Expression of brain-derived neurotrophic factor in cortical neurons is regulated by striatal target area

Changes in BDNF expression after different types of brain insults are relat ed to neuroprotection, stimulation of sprouting, and synaptic reorganizatio n. In the cerebral cortex, an autocrine-paracrine mechanism for BDNF has be en proposed because the distribution patterns of BDNF and TrkB expression a re almost identical. Moreover, cortical BDNF is anterogradely transported t o the striatum, suggesting a role of BDNF in the functional interaction bet ween the two brain regions. Here we have examined the expression of this ne urotrophin in the cerebral cortex after various striatal lesions. Intrastri atal injection of quinolinate, kainate, 3-nitropropionic acid, or colchicin e increased BDNF mRNA levels in cerebral cortex. In contrast, stimulation o f neuronal activity in the striatum did not change cortical BDNF expression . Both excitatory amino acids increased BDNF expression in neurons of corti cal layers II/III, V, and VI that project to the striatum. Moreover, grafti ng a BDNF-secreting cell line prevented both the loss of striatal neurons a nd the cortical upregulation of BDNF induced by excitotoxins. Because retro grade transport in the corticostriatal pathway was intact after striatal le sions, our results suggest that striatal damage upregulates endogenous BDNF in corticostriatal neurons by a transneuronal mechanism, which may constit ute a protective mechanism for striatal and/or cortical cells.