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

Abstract

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.

Gene co-expression architecture in peripheral blood in a cohort of remitted first-episode schizophrenia patients

“…Both biological processes have been shown to play a vital role in neuronal growth and differentiation, as well as in neuronal survival, synaptogenesis, and neuroplasticity in the adult brain 32 , 33 . Complex crosstalk between these processes has been proposed and could form the neurobiological basis of schizophrenia through the cellular communication between astrocytes and microglia 34 – 36 . A notable gene in the network is furin, a paired basic amino acid cleaving enzyme ( FURIN ), one of the loci that showed a significant overlap between GWAS for schizophrenia and eQTL in the DLPFC reported by Fromer et al 7 .…”

Cracking the Code of Neuronal Cell Fate

“…Before this “commitment point”, apoptosis of CGNs can be rescued following the activation of specific signal transduction pathways or by the administration of NFs [ 9 , 30 ]. Over the past 20 years, our research groups and others have begun to explore the transcriptional changes during the pre-commitment phase of apoptosis and its rescue by different NFs [ 6 , 9 , 10 , 22 , 23 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. Taken together, these studies highlighted that, although distinct NFs exert their survival effects by binding specific receptors and activating a plethora of intracellular second messengers, their signaling pathways share striking similarities and are propagated by common transcriptional cascades, suggesting the existence of a conserved transcriptional program at the intersection of apoptosis and survival.…”