ERK and SAPK signaling in auditory brainstem neurons after unilateral cochlear ablation.
Unilateral cochlear ablation (UCA) in adults deafferented one cochlear nucleus (CN) and induced several plasticities in central auditory pathways. To assess whether signal transduction could contribute to these changes, we determined if UCA induced activity in the extracellular signal-regulated kinase (ERK) and the stress-activated protein kinase (SAPK) signal transduction pathways. Using Western blots, we measured phosphorylated ERK1 (ERK1-P), ERK2 (ERK2-P), p46 and p54 SAPK (SAPK-P) and c-Jun (c-Jun-P) levels in the major subdivisions of the CN, the principal nuclei of the superior olivary complex (SOC) and the central nucleus of the inferior colliculus (ICc) for up to 145 days postablation. ERK1-P and ERK2-P were typically elevated at 7 and 145 days but depressed at 30 days, 60 days, or both. In addition, ERK1-P and ERK2-P were elevated at 3 days in the anteroventral (AVCN) and posteroventral CN (PVCN). Immunohistochemical labeling indicated that after 5 days, most ERK1/2-P in the CN was in neuronal nuclei. Only minor changes were evident in total ERK1 and ERK2 levels. Several correlations were evident between the postablation plasticities observed previously and altered ERK1-P and ERK2-P levels. Few changes were found in SAPK-P and c-Jun-P levels. Concomitant elevations of SAPK-P and c-Jun-P were not evident, except in the superficial dorsal CN (DCN) at postablation day 3, consistent with a cell-stress response. These findings suggest that signals induced as a consequence of UCA are transduced mainly through the neuronal ERK pathway. This activity probably influenced gene expression and cytoplasmic regulatory mechanisms that contributed to the plasticities induced by UCA.
Suneja
Sanoj K
SK
Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030, USA. ssuneja@neuron.uchc.edu
Potashner
Steven J
SJ
D000818:Animals; D001933:Brain Stem / Q000737:chemistry / Q000201:enzymology*; D017626:Cochlear Nucleus / Q000737:chemistry / Q000201:enzymology* / Q000293:injuries*; D005260:Female; D006168:Guinea Pigs; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000737:chemistry / Q000201:enzymology*; D010766:Phosphorylation
D020928:Mitogen-Activated Protein Kinases