The effects of different auditory activity on the expression of phosphorylated c-Jun in the auditory system.
CONCLUSIONS
The data revealed that calcium influx via the NMDA receptor up-regulated the expression of phosphorylated c-Jun in the primary auditory cortices following sensory stimulation and after different neural injury stimulations which guide activity-dependent changes in gene expression and neural plasticity.


OBJECTIVE
Activator protein-1 (AP-1) transcription factor, which is mainly composed of c-Fos and c-Jun proteins, is believed to be a key participant in molecular processes that guide activity-dependent changes in gene expression. Our previous study had shown that the expression of NMDAR2A gene on synaptosomes membrane of auditory cortical neurons varied by electrical intracochlear stimulation (EIS) and neural injury induced by acoustic trauma. In this study, we investigated the role of the NMDA receptor (NMDAR) in regulating the expression of phosphorylated c-Jun in the primary auditory cortex (AI). The modulation factors observed for gene expression included EIS and noise traumas.


METHODS
EIS was applied in rats with early postnatal auditory deprivation. The impact of the noise traumas on the ultrastructures of spiral ganglion neurons (SGNs) and their innervations to inner hair cells (IHCs) were verified by transmission electron microscopy (EM). These changes include a decrease in subcellular organelles, the swelling of mitochondria and endoplasmic reticulum, the morphological changes in cell nuclei, and damage in the afferent synapse.


RESULTS
Immunohistochemistry observations showed that the expression of phosphorylated c-jun and active caspase-3 in hair cells and SGNs varied with amount of noise. Immunocytochemistry and Western blotting showed that the auditory cortex began to express phosphorylated c-jun 24 h after 2 h of EIS. However, this expression was not changed by EIS if NMDAR antagonist was applied. The level of phosphorylated c-Jun was remarkably increased in AI after noise overstimulation at 115 dB SPL for 3 h. Again, such an increase was not seen if NMDAR antagonist 3-(2 carboxypiperazin-4yl) propyl-1-phosphonic acid (CPP, 10 mg/kg, i.p.) was applied 30 min before the noise exposure.
Ruan
Qingwei
Q
Otolaryngology Research Institute, Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, PR China.
Wang
Dehui
D
Gao
Hongyang
H
Liu
Aiguo
A
Da
Cuidi
C
Yin
Shankai
S
Chi
Fanglu
F
D000818:Animals; D001303:Auditory Cortex / Q000473:pathology / Q000502:physiology*; D001306:Auditory Pathways / Q000502:physiology; D001309:Auditory Threshold / Q000502:physiology; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D003051:Cochlea / Q000378:metabolism / Q000648:ultrastructure; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D016758:Genes, jun; D006317:Hearing Loss, Noise-Induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D009473:Neuronal Plasticity / Q000502:physiology; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D016755:Proto-Oncogene Proteins c-jun; D016194:Receptors, N-Methyl-D-Aspartate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D053148:Caspase 3