Neuronal Expression of Tumor Necrosis Factor Alpha in the OVOUJI fme Brain

Abstract

We have examined the expression of the inflammatory cytokine, tumor necrosis factor alpha (TNFα) in the mouse brain. Using immunohistochemical methods developed, we found anti-TNFα immunoreactivity localized in the basal ganglia and other discrete brain structures. Constitutive immunoreactivity, present in normal, unstimulated brain, was observed in glial and microglial-like cells, but it was predominant in neuronal-like cells. Intravenous administration of lipopolysaccharide (LPS) increased TNFα transcript levels detected by RT-PCR in specific brain subregions in which contaminating blood cells were removed. The maximal increase occurred within 2 h of LPS injection; transcripts diminished to near control levels in the next 4 h. Immunocytochemical analysis and single-cell RT-PCR analysis of primary cultures of cortical neuronal cells confirmed expression of TNFα in cells that also express neuronal-specific enolase RNA. Addition of LPS or recombinant TNFα protein to neuronal cultures enhanced expression of TNFα transcripts. Our results indicate that in addition to glial and microglial cells, a well-defined subset of neuronal cells also express TNFα constitutively; this expression can be altered by both extrinsic (LPS) and intrinsic (TNFα itself) factors.