Regional susceptibility to TNF-alpha induction of murine brain inflammation via classical IKK/NF-kappa B signalling

Abstract

It is becoming clear that inflammation plays a significant role in a number of neurological and psychiatric conditions. Post mortem brain samples in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, schizophrenia and most recently autism spectrum condition, all exhibit neuroglial activation and inflammatory markers within the CSF. Many questions remain about the underlying molecular mechanisms. By adding the pro-inflammatory cytokine, TNF-alpha, to mouse brain tissue we demonstrated that the frontal lobes and temporal region, areas involved in higher functions such as memory and learning, are most susceptible to cytokine-induced inflammation via the NF-kappa B signalling pathway. We observed direct correlations between the volumetric increase and molecular expression indicating that therapeutic targets in these lobes may require different approaches when treating conditions with a central neuroinflammatory component.