The trophic effect of nerve growth factor in primary cultures of rat hippocampal neurons is associated to an anti-inflammatory and immunosuppressive transcriptional program.

Nerve growth factor, the prototype of a family of neurotrophins, elicits differentiation and survival of peripheral and central neuronal cells. Although its neural mechanisms have been studied extensively, relatively little is known about the transcriptional regulation governing its effects. We have previously observed that in primary cultures of rat hippocampal neurons treatment with nerve growth factor for 72 hr increases neurite outgrowth and cell survival. To obtain a comprehensive view of the underlying transcriptional program, we performed whole-genome expression analysis by microarray technology. We identified 541 differentially expressed genes and characterized dysregulated pathways related to innate immunity: the complement system and neuro-inflammatory signaling. The exploitation of such genes and pathways may help interfering with the intracellular mechanisms involved in neuronal survival and guide novel therapeutic strategies for neurodegenerative diseases.