Enrofloxacin exposure enhances GABA synthesis via PI3K/Akt signaling pathway in crucian carp brain.

It has been proved that enrofloxacin (ENR) induces disturbance of neuroendocrine system, resulting in reproductive damage in animals and fish. Our previous work revealed that ENR promoted testosterone (T) synthesis but inhibited the conversion of T to E in crucian carp. The toxicological mechanism involves HPG axis, secretoneurin A (SNa) and aromatase, but the upstream mechanism is still unknown. To further explore the molecular mechanism, this study investigated the effect of ENR on metabolism of γ-aminobutyric acid (GABA) in female crucian carp brain. Fish exposed to ENR and/or PI3K inhibitor LY249002 were detected contents of GAGA and Glu, expression of glutamic acid decarboxylase (GAD) and GABA transaminase (GABA-T) expression, and contents of TCA cycle products and bioamines, as well as expression and activation of Akt protein in brain of crucian carp, using detection kits, qPCR, immunohistochemical analysis and ultra performance liquid chromatography, respectively. Data show that ENR promoted GABA synthesis from Glu in the shunt route through activating PI3K/Akt signaling pathway to upregulate GAD and GABA-T expression, resulting in accumulation of GABA and acetyl-CoA. Consequently, GABA stimulated the anabolic pathway of T via SNa associated pathways, thereby accelerated T synthesis from acetyl-CoA. These results indicate a new perspective for learning toxicological mechanism of ENR induced disorder of the neuroendocrine system and reproductive injury in animal.