BDNF RESTORES THE EXPRESSION OF JUN AND FOS INDUCIBLE TRANSCRIPTION FACTORS IN THE RAT-BRAIN FOLLOWING REPETITIVE ELECTROCONVULSIVE SEIZURES

The expression of inducible transcription factors was studied followin g repetitive electroconvulsive seizures (ECS), c-Fos, c-Jun, JunB, and JunD immunoreactivities were investigated following a single (Ix ECS) or repetitive ECS evoked once per day for 4, 5, or 10 days (4xECS, 5x ECS, or 10xECS). Animals were billed 3 or 12 h following the last ECS. Three hours after 1xECS, c-Fos was expressed throughout the cortex an d hippocampus. After 5xECS and 10xECS, c-Fos was reexpressed in the CA 4 area, but was completely absent in the other hippocampal areas and c ortex. In these areas, c-Fos became only reinducible when the time lag between two ECS stimuli was 5 days. In contrast to c-Fos, intense Jun B expression was inducible in the cortex and hippocampus, but not CA4 subfield, after 1xECS, 5xECS, and 10xECS. Repetitive ECS did not effec t c-Jun and JunD expression. In a second model of systemic excitation of the brain, repetitive daily injection of kainic acid for 4 days com pletely failed to express c-Fos, c-Jun, and JunB after the last applic ation whereas injection of kainic acid once per week did not alter the strong expressions compared to a single application of kainic acid. I n order to study the maintenance of c-Fos expression during repetitive seizures, brain-derived neurotrophic factor (BDNF) was applied in par allel for 5 or 10 days via miniosmotic pumps and permanent cannula tar geted at the hippocampus or the parietal cortex. Infusion of BDNF comp letely reinduced c-Fos expression during 5xECS or 10xECS in the cortex ipsilaterally to the cannula and, to a less extent, also increased th e expression of c-Jun and JunB when compared to saline-treated control s. BDNF had no effect on the expression patterns in the hippocampus. E CS with or without BDNF infusion did not change the expression pattern s of the constitutive transcription factors ATF-2, CREB, and SRF. Thes e data demonstrate that various transcription factors substantially di ffer in their response to acute and chronic neural stimulation, Repeti tive pathophysiological excitation decreases the transcriptional actio ns of neurons over days in the adult brain, and this decrement can be prevented by BDNF restoring the neuroplasticity at the level of gene t ranscription. (C) 1998 Academic Press.