Changes in the expression level of MAPK pathway components induced by monosodium glutamate-administration produce neuronal death in the hippocampus from neonatal rats

Abstract

Excessive Glutamate (Glu) release may trigger excitotoxic cellular death by the activation of intracellular signaling pathways that transduce extracellular signals to the cell nucleus, which determines the onset of a death program. One such signaling pathway is the mitogen-activated protein kinases (MAPK), which is involved in both survival and cell death. Experimental evidences from the use of specific inhibitors supports the participation of some MAPK pathway components in the excitotoxicity mechanism, but the complete process of this activation, which terminates in cell damage and death, is not clearly understood. The present work, we investigated the changes in the expression level of some MAPK-pathway components in hippocampal excitotoxic cell death in the neonatal rats using an experimental model of subcutaneous monosodium glutamate (MSG) administration on postnatal days (PD) 1, 3, 5 and 7. Data were collected at different ages through PD 14. Cell viability was evaluated using fluorescein diacetate mixed with propidium iodide (FDA-PI), and the Nissl-staining technique was used to evaluate histological damage. Transcriptional changes were also investigated in 98 components of the MAPK pathway that are associated with cell damage. These results are an evidence of that repetitive use of MSG, in neonatal rats, induces cell damage-associated transcriptional changes of MAPK components, that might reflect a differential stage of both biochemical and molecular brain maturation. This work also suggests that some of the proteins evaluated such as phosphorylated retinoblastoma (pRb) protein, which was up-regulated, could regulate the response to excitotoxic through modulation of the process of re-entry into the cell cycle in the hippocampus of rats treated with MSG.

Keywords: MAPK; MSG; excitotoxicity; gene expression; hippocampus.