Pathophysiology of the glutamatergic synapses in the cochlea.
The synapses between the inner hair cells (IHCs) and the radial auditory dendrites are thought to be glutamatergic. Besides its fast excitatory properties, glutamate is known to be neurotoxic when released in excess or incompletely recycled. In the cochlea, this may occur in two pathological conditions: ischemia and noise trauma. We have further investigated the acute excitotoxicity (i.e. the swelling of type I afferent dendrites) by electron microscopy processing on guinea pig cochleas after an ischemic exposure lasting 5 to 40 min. The radial auditory dendrites reacted to ischemia in a time-dependent manner, with the swelling extending when the duration of ischemia increased. The type and the specificity of swelling were comparable to what acutely occurs after an exposure to glutamate analogs such as kainic acid or AMPA. A protection against this swelling was obtained by perfusing the cochlea with glutamate antagonists prior to ischemia. DNQX, an antagonist at AMPA/kainate receptors, had a powerful protective effect, and almost complete protection was obtained by perfusing both DNQX and D-AP5 (a NMDA antagonist). The latter results indicate that the two classes of glutamate receptors (AMPA/kainate and NMDA), both found to be electrophysiologically active at the IHC-auditory nerve synapse, are also involved in the excitotoxic processes. In addition, we also report data involving dopamine (its D2 agonist piribedil) a putative neurotransmitter at the lateral efferent synapses, in a postsynaptic protection of primary auditory neurons during transient ischemia. Altogether, these findings constitute a promising pharmacological approach of cochlear pathologies such as neural presbycusis.
Pujol
R
R
INSERM U.-254, Laboratoire de Neurobiologie de l'Audition, Hôpital St. Charles, Montpellier, France.
Puel
J L
JL
Gervais d'Aldin
C
C
Eybalin
M
M
D000818:Animals; D003051:Cochlea / Q000098:blood supply / Q000294:innervation*; D003712:Dendrites / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D005971:Glutamates / Q000502:physiology*; D018698:Glutamic Acid; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000503:physiopathology*; D007511:Ischemia / Q000503:physiopathology; D010891:Piribedil / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D000159:Vestibulocochlear Nerve / Q000502:physiology
D005971:Glutamates; D011810:Quinoxalines; D017470:Receptors, Glutamate; D018698:Glutamic Acid; C056723:FG 9041; D010891:Piribedil; D004298:Dopamine