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Updated: Aug 18, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Microglia-derived tumor necrosis factor-alpha exaggerates death of newborn hippocampal progenitor cells in vitro
Emanuele Cacci1, Jan-Hendrik Claasen, Zaal Kokaia
1Laboratory of Neural Stem Cell Biology, Section of Restorative Neurology, University Hospital, and Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Sweden.
Abstract:
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.
Insights
Activated microglia release tumor necrosis factor-alpha (TNFα), a cytokine that triggers cell death in new hippocampal progenitor cells (HPCs). This finding is crucial for understanding brain injury responses.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Adult mammals generate new hippocampal neurons, but many hippocampal progenitor cells (HPCs) perish early.
- Brain insults can increase neurogenesis, yet progenitor cell survival remains a challenge.
Purpose of the Study:
- To investigate if cytokines released by activated microglia contribute to the death of HPCs.
- To determine the role of tumor necrosis factor-alpha (TNFα) in HPC apoptosis.
Main Methods:
- Cultured HPC line (HiB5) exposed to TNFα and conditioned medium from activated/non-activated microglial cell lines (BV-2).
- Reverse transcription-PCR to detect TNF receptor expression (TNF-R1, TNF-R2) in HPC and microglial cells.
- Co-culturing experiments with HPCs and activated microglia.
Main Results:
- TNFα induced significant apoptotic cell death in cultured HPCs.
- Conditioned medium from activated microglia mimicked TNFα's effect, while medium from non-activated microglia promoted HPC survival.
- Both HPCs and microglia express TNF receptors (TNF-R1, TNF-R2).
- Co-culturing with activated microglia increased HPC death and also caused microglial cell death.
Conclusions:
- Activated microglia-released TNFα may significantly contribute to inflammation-induced death of newly formed HPCs in the adult brain post-insult.
- Understanding this mechanism is vital for developing strategies to protect newly formed neurons after brain injury.
