6533b7d9fe1ef96bd126c29a
RESEARCH PRODUCT
LPS-induced microglial secretion of TNFα increases activity-dependent neuronal apoptosis in the neonatal cerebral cortex.
Shuming AnRobin WhiteHeiko J. LuhmannJyh-jang SunJenq-wei YangBirgit NimmervollChristopher Hennsubject
LipopolysaccharidesProgrammed cell deathCognitive NeuroscienceBlotting WesternInflammationApoptosisBiologyCellular and Molecular NeuroscienceCortex (anatomy)medicineAnimalsRats WistarMacrophage inflammatory proteinCerebral CortexInflammationNeuronsMicrogliaTumor Necrosis Factor-alphaCell biologyRatsElectrophysiologymedicine.anatomical_structureAnimals NewbornApoptosisCerebral cortexImmunologyTumor necrosis factor alphaMicrogliamedicine.symptomdescription
During the pre- and neonatal period, the cerebral cortex reveals distinct patterns of spontaneous synchronized activity, which is critically involved in the formation of early networks and in the regulation of neuronal survival and programmed cell death (apoptosis). During this period, the cortex is also highly vulnerable to inflammation and in humans prenatal infection may have a profound impact on neurodevelopment causing long-term neurological deficits. Using in vitro and in vivo multi-electrode array recordings and quantification of caspase-3 (casp-3)-dependent apoptosis, we demonstrate that lipopolysaccharide-induced inflammation causes rapid alterations in the pattern of spontaneous burst activities, which subsequently leads to an increase in apoptosis. We show that these inflammatory effects are specifically initiated by the microglia-derived pro-inflammatory cytokine tumor necrosis factor α and the chemokine macrophage inflammatory protein 2. Our data demonstrate that inflammation-induced modifications in spontaneous network activities influence casp-3-dependent cell death in the developing cerebral cortex.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-06-16 | Cerebral cortex (New York, N.Y. : 1991) |