Glutamate neurotoxicity in the cochlea: a possible consequence of ischaemic or anoxic conditions occurring in ageing.
Glutamate is considered to be one of the most common neurotransmitters in the fast excitatory synapses in the central nervous system. On the other hand, its excitotoxic properties are increasingly cited to explain some of the brain damage linked with hypoxia and ischaemia: i.e., those that occur frequently in ageing. An excess release of glutamate could, either directly or indirectly, activate receptors on the postsynaptic neuron, causing ion influxes accompanied by a massive entry of water, which would lead to an acute swelling of dendrites. In addition, calcium influx deregulates calcium homeostasis, which could lead to cell death. In the cochlea, glutamate is now considered to be one of the best candidates to mediate neurotransmission between inner hair cells (IHCs) and the auditory nerve dendrites. Among the variety of anatomical and physiological findings supporting the glutamate hypothesis, is the striking similarity of acute damage in the organ of Corti caused by exposure to a glutamate analogue (kainic acid), or by hypoxia, or even by an intense loud noise. In all cases an immediate swelling is observed, specifically affecting the radial afferents below the IHCs. The best explanation for this swelling is related to glutamate (or glutamate analogue) excitotoxicity. Thus, some of the cochlear damage that occur with ageing, especially the loss of the radial afferent fibres and type I ganglion cells, might well be attributed to glutamate excitotoxicity linked to vascular atrophy. The present paper discusses this hypothesis.
Pujol
R
R
INSERM-U. 254, Laboratoire de Neurobiologie de l'Audition, Hopital St. Charles, Montpellier, France.
Rebillard
G
G
Puel
J L
JL
Lenoir
M
M
Eybalin
M
M
Recasens
M
M
D000375:Aging / Q000473:pathology*; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D003051:Cochlea / Q000187:drug effects*; D005971:Glutamates / Q000009:adverse effects* / Q000502:physiology; D018698:Glutamic Acid; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000502:physiology; D006801:Humans; D007511:Ischemia / Q000503:physiopathology; D007608:Kainic Acid / Q000009:adverse effects; D018377:Neurotransmitter Agents / Q000502:physiology; D011304:Presbycusis / Q000209:etiology*; D000159:Vestibulocochlear Nerve / Q000502:physiology
D005971:Glutamates; D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D007608:Kainic Acid