Early postnatal ethanol exposure selectively decreases BDNF and truncated TrkB-T2 receptor mRNA expression in the rat cerebellum

Binge-like ethanol exposure on postnatal day (PN) 4 induces a concentration dependent loss of Purkinje cells in the rat cerebellum. The mechanism of t his ethanol-induced Purkinje cell vulnerability is not presently understood . Nevertheless, the specific timing of this vulnerability leads us to consi der the neurotrophin system crucial to the regulation of neuronal developme nt. Differentiation, maturation, and survival of Purkinje cells are shown t o involve an intimate interaction between brain-derived nerve growth factor (BDNF) and neurotrophin-3 (NT3) acting primarily through their specific ty rosine-kinase (Trk) receptors. We believe that the specific ethanol vulnera bility, and the timing of this vulnerability result from alterations in the BDNF-NT3 interplay. We hypothesize that disruption of TrkB and/or TrkC med iated neurotrophin communication is, in part. responsible for the ethanol-i nduced loss of Purkinje cells during development. The current study was und ertaken to define the impact of ethanol exposure at the onset of ethanol vu lnerability on the relative concentrations of mRNA encoding the neurotrophi c factor receptors TrkB and TrkC. The reverse transcriptase (RT) polymerase chain reaction (PCR) amplification technique was used to identify the rela tive expression levels of mRNA specific to these receptors as well as the t runcated TrkB; receptor isoforms. We identify a specific decrease in overal l TrkB receptor mRNA expression that is primarily a function of the TrkB-T2 receptor isoform. Concurrent decreases in mRNA specific to BDNF were also identified. No significant alterations to the expression of TrkC mRNA were found indicating that ethanol-exposure appears to act selectively on the BD NF communication system. (C) 2001 Elsevier Science B.V. All rights reserved .