Imipramine activates glial cell line-derived neurotrophic factor via early growth response gene 1 in astrocytes

►Egr-1 binding sequences in the GDNF promoter are necessary for optimal promoter activation by imipramine. ►Induction of Egr-1 by imipramine upregulate GDNF in a dose-dependent manner. ►Imipramine-induced GDNF mRNA expression was strongly attenuated in primary astrocytes from Egr-1−/− mice. ►Imipramine induction of Egr-1 occur through the MEK/ERK and JNK MAPK pathways in astrocytes.