Microglia-derived tumor necrosis factor ? exaggerates death of newborn hippocampal progenitor cells in vitro

Production of new hippocampal neurons continues in adult mammals and different brain insults can significantly increase this process. However, many hippocampal progenitor cells (HPC) die shortly after birth. Here we investigated the possibility that increased release of cytokines by activated microglia contributes to the death of HPC. We showed that addition of tumor necrosis factor-alpha (TNFalpha) to the medium of a cultured HPC line (HiB5) shortly after the cells stopped division causes significant apoptotic cell death. Conditioned medium from an activated microglial cell line (BV-2) had a similar effect, though conditioned medium from nonactivated microglia increased the survival of HPC. Reverse transcription-PCR indicated that HPC and microglial cells express both TNF receptors, TNF-R1 and TNF-R2. Coculturing of HPC with activated microglial cells aggravated death of hippocampal progenitors and also caused death of microglial cells themselves. Our data indicate that activated microglia-released TNFalpha might be an important contributor in inflammation-induced exaggeration of death of newly formed HPC in the adult brain after an insult.