Protein kinase C may be involved in synaptic repair of auditory neuron dendrites after AMPA injury in the cochlea.
A suitable model of sudden deafness occurring after acoustic trauma or ischemia, is obtained in guinea pigs by an acute intracochlear perfusion of 200 microM alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), a glutamate analog. By overloading the AMPA/kainate receptors, located post-synaptically to inner hair cells (IHCs), it induces a massive swelling of primary auditory neuron dendrites, which disconnects the IHCs. This synaptic uncoupling and the resulting hearing loss are followed by a progressive regrowth of dendrites, which make new synapses with IHCs, leading to a functional recovery of auditory responses that is completed after 5 days. Knowing the role of protein kinase C in neuroplastic events, we studied the expression of its isoforms alpha,beta(I,II) and gamma, respectively pre- and post-synaptic, in auditory neurons at various times after AMPA administration. In untreated cochleas, we observed an expression of PKC alpha,beta(I,II) and gamma in cell bodies of primary auditory neurons. After the intracochlear administration of AMPA, both isozymes were transiently overexpressed, with a peak at 3-6 h, followed by a decrease after about 24 h. At this point in time immuno-electron microscopy revealed some regrowing dendrites immunoreactive for PKCgamma. Five days after AMPA, when the auditory responses were restored, PKCgamma levels were still elevated in ganglion cell bodies.
Lerner-Natoli
M
M
INSERM U254 and Université de Montpellier I, CHU Hôpital St Charles, France.
Ladrech
S
S
Renard
N
N
Puel
J L
JL
Eybalin
M
M
Pujol
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015834:Cochlear Diseases / Q000139:chemically induced* / Q000473:pathology; D003712:Dendrites / Q000502:physiology* / Q000648:ultrastructure; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005260:Female; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000502:physiology / Q000648:ultrastructure; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology*; D008297:Male; D016253:Microscopy, Immunoelectron; D009473:Neuronal Plasticity / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology* / Q000648:ultrastructure; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000633:toxicity
D000911:Antibodies, Monoclonal; D018690:Excitatory Amino Acid Agonists; D007527:Isoenzymes; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D011493:Protein Kinase C