Taurine improves the differentiation of neural stem cells in fetal rats with intrauterine growth restriction via activation of the PKA-CREB-BDNF signaling pathway.

ABSTRACT

Intrauterine growth restriction (IUGR) affects brain neural stem cell (NSC) differentiation. In the present study, we investigated whether taurine supplementation may improve NSC differentiation in IUGR fetal rats via the protein kinase A-cyclic adenosine monophosphate (cAMP) response element protein-brain derived neurotrophic factor (PKA-CREB-BDNF) signaling pathway. The IUGR fetal rat model was established with a low-protein diet. Fresh subventricular zone (SVZ) tissue from the fetuses on the 14th day of pregnancy was microdissected and dissociated into single-cell suspensions, then was cultured to form neurospheres. The neurospheres were divided into the control group, the IUGR group, the IUGR+taurine (taurine) group, the IUGR+H89 (H89) group and the IUGR+taurine+H89 (taurine+H89) group. The mRNA and protein expression levels of PKA, CREB and BDNF were measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting (WB). Tuj-1-positive neurons and GFAP-positive glial cells were detected by immunofluorescence. The total number of proliferating NSCs and the percentage of Tuj-1-positive neurons in the IUGR group were lower than those in the control group, but the percentage of GFAP-positive cells was higher in the IUGR group than in the control group. Taurine supplementation increased the total number of neural cells and the percentage of Tuj-1-positive neurons, and reduced the percentage of GFAP-positive cells among differentiated NSCs after IUGR. H89 reduced the total number and percentage of Tuj-1-positive neurons and increased the percentage of GFAP-positive cells. The mRNA and protein levels of PKA, CREB, and BDNF were lower in the IUGR group. The mRNA and protein expression levels of these factors were increased by taurine supplementation but reduced by the addition of H89. Taurine supplementation increased the ratio of neurons to glial cells and prevented gliosis in the differentiation of NSCs in IUGR fetal rats by activating the PKA-CREB-BDNF signaling pathway.