Overexpression of neuropeptide Y induced by brain-derived neurotrophic factor in the rat hippocampus is long lasting

Brain-derived neurotrophic factor (BDNF) plays an important role in hippoca mpal neuroplasticity. In particular, BDNF upregulation in the hippocampus b y epileptic seizures suggests its involvement in the neuronal rearrangement s accompanying epileptogenesis. We have shown previously that chronic infus ion of BDNF in the hippocampus induces a long-term delay in hippocampal kin dling progression. Although BDNF has been shown to enhance the excitability of this structure upon acute application, long-term transcriptional regula tions leading to increased inhibition within the hippocampus may account fo r its suppressive effects on epileptogenesis. Therefore, the long-term cons equences of a 7-day chronic intrahippocampal infusion of BDNF (12 mu g/day) were investigated up to 2 weeks after the end of the infusion, on the expr ession of neurotransmitters contained in inhibitory hippocampal interneuron s and which display anti-epileptic properties. Our results show that BDNF d oes not modify levels of immunostaining for glutamic acid decarboxylase, th e rate-limiting enzyme for gamma-aminobutyric acid (GABA) synthesis, and so matostatin. Conversely, BDNF induces a long-lasting increase of neuropeptid e Y (NPY) in the hippocampus, measured by immunohistochemistry and radioimm unoassay, outlasting the end of the infusion by at least 7 days. The distri bution of BDNF-induced neuropeptide Y immunoreactivity is similar to the pa ttern observed in animals submitted to hippocampal kindling, with the excep tion of mossy fibres which only become immunoreactive following seizure act ivity. The enduring increase of neuropeptide Y expression induced by BDNF i n the hippocampus suggests that this neurotrophin can trigger long-term gen omic effects, which may contribute to the neuroplasticity of this structure , in particular during epileptogenesis.