Is related the hematopoietic stem cells differentiation in the Nile tilapia with GABA exposure?

The signaling mediated by small non-proteinogenic molecules, which probably have the capacity to serve as a bridge amongst complex systems is one of the most exiting challenges for the study. In the current report, stem cells differentiation of the immune system in Nile tilapia treated with sub-basal doses of GABA evaluated as c-kit+ and Sca-1+ cells disappearance on pronephros, thymus, spleen and peripheral blood mononuclear cells by flow cytometry was assessed. Explanation of biological response was performed by molecular docking approach and multiparametric analysis. Stem cell differentiation depends on a delicate balance of negative and positive interactions of this neurotransmitter with receptors and transcription factors involved in this process. This in turn depends on the type of interaction with hematopoietic niche to differentiate into primordial, early or late hematopoiesis as well as from the dose delivery. In fish treated with the low doses of GABA (0.1% over basal value) primordial hematopoiesis is regulated by interaction of glutamate (Glu) with the Ly-6 antigen. Early hematopoiesis was influenced by the bond of GABA near or adjacent to turns of FLTR3-Ig-IV domain. During late hematopoiesis, negative regulation by structural modifications on PU.1/IRF-4 complex, IL-7Rα and GM-CSFR mainly prevails. Results of molecular docking were in agreement with the percentages of the main blood cells lineages estimated in pronephros by flow cytometry. Current study provides the first evidences about the role of inhibitory and excitatory neurotransmitters such as GABA and Glu, respectively with the most transcriptional factors and receptors involved on hematopoiesis in adult Nile tilapia.

Sub-basal increases of GABA enhance the synthesis of TNF-α, TGF-ß, and IL-1ß in the immune system organs of the Nile tilapia.

The cells of the immune and neuronal systems share different receptors for cytokines or neurotransmitters, producing feedback responses between both systems. Cytokines such as IL-1ß and TNF-α can induce inflammation; however, the secretion of these molecules can be modulated by anti-inflammatory cytokines, as is the case for TGF-ß, as well as by different hormones or neurotransmitters such as the γ-aminobutyric acid (GABA). In this study, we evaluated the secretion of IL-1ß, TNF-α, and TGF-ß under basal conditions, in the head of the kidney, spleen, thymus, and serum of the Nile tilapia, as well as their release induced by different sub-basal increases of GABA. We found that at the higher dose of GABA these cytokines were synthesised at a higher concentration compared to the control group. These results may suggest that there is feedback between both systems and that GABA plays a role in the modulation of the immune response.