Bita Firozan, IranGoudarzi , MahmoudElahdadi, TaghiLashkarbolouki, Arezou Rezaei, KatanehAbrari
European Journal of Pharmacology
Publication year:

Abstract

Binge-like ethanol exposure on postnatal day (PN) 4 induces a concentration dependent loss of Purkinje cells in the rat cerebellum. The mechanism of this ethanol-induced Purkinje cell vulnerability is not presently understood. Nevertheless, the specific timing of this vulnerability leads us to consider the neurotrophin system crucial to the regulation of neuronal development. Differentiation, maturation, and survival of Purkinje cells are shown to involve an intimate interaction between brain-derived nerve growth factor (BDNF) and neurotrophin-3 (NT3) acting primarily through their specific tyrosine-kinase (Trk) receptors. We believe that the specific ethanol vulnerability, and the timing of this vulnerability result from alterations in the BDNF-NT3 interplay. We hypothesize that disruption of TrkB and/or TrkC mediated neurotrophin communication is, in part, responsible for the ethanol-induced loss of Purkinje cells during development. The current study was undertaken to define the impact of ethanol exposure at the onset of ethanol vulnerability on the relative concentrations of mRNA encoding the neurotrophic factor receptors TrkB and TrkC. The reverse transcriptase (RT) polymerase chain reaction (PCR) amplification technique was used to identify the relative expression levels of mRNA specific to these receptors as well as the truncated TrkB receptor isoforms. We identify a specific decrease in overall 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 BDNF communication system.