The effects of the glial cell line-derived neurotrophic factor (GDNF) on the levels of mRNA of apoptotic genes Bax and Bcl-xl in the brain of mice genetically predisposed to pathological behavior

Abstract

Similar to the other neurotrophic factors, the glial cell line-derived neurotrophic factor (GDNF) may inhibit apoptosis in vitro. However, the antiapoptotic GDNF effects in vivo are not known. We studied the effect of GDNF central administration of on the mRNA levels of genes encoding the proapoptotic protein Bax and the antiapoptotic protein Bcl-xl in the brain of ASC mice genetically predisposed to depressivelike behavior and mice of their nondepressive parental CBA strain. We found that the GDNF injection increased the Bcl-xl mRNA content in the hippocampi of mice of both strains (ρ < 0.05) and Bax mRNA (ρ < 0.05) in the hippocampus of ASC mice. Thus, we revealed both the antiand proapoptotic effects of GDNF in vivo. These effects substantially depended on the genotype of the animals. We also observed significant interstrain differences in the Bax and Bcl-xl mRNA levels. In ASC mice, the Bax mRNA levels were significantly higher (ρ < 0.001 and ρ < 0.01) in all investigated structures and the content of Bcl-xl mRNA was elevated in the midbrain. Our data demonstrate the activation of apoptotic processes in ASC mice and the substantial compensatory changes, probably directed to the rise of the threshold for neuronal apoptosis.