Glutamate induces apoptosis in cultured spiral ganglion explants
Section snippets
Materials and methods
Preparation of spiral ganglion explants. All animal experiments were approved by the local administration (Regierung Oberbayern, Munich, No. 211–25314/2002). The preparation of the spiral ganglion explants was performed as described [14], [15], [16] using gerbils (Charles River, Sulzfeld, Germany) at day 4 post-natal. After cervical transfection the heads of the gerbils were skinned, the skulls were opened midsagittally, and the brain halves were removed. The following steps were carried out
Glutamate induces apoptosis in cultured spiral ganglion explants
Fig. 1a shows a typical spiral ganglion explant incubated with culture medium for 48 h and stained by immunohistochemistry for detecting neurofilament. The neurites extend from the spiral ganglion explant edge. Near the edge they form fascicles and further away they split into individual fibers. The neurites are adjacent to non-neuronal cells, which seem to be glial cells and fibroblasts. If the spiral ganglion explants are incubated with 5 mM glutamate for 48 h, the extension of the neurites as
Discussion
Glutamate exposure to spiral ganglion explants reduced the length of neurites and led to apoptosis of the spiral ganglion neurons depending on the glutamate concentration. This is the first study that directly shows that apoptosis is induced by the neurotoxic effect of high concentrations of glutamate on neurites and spiral ganglion cells.
This is in congruence with observations of Janssen et al. [4]. In his study post-natal treatment with glutamate in rats (4 g glutamate/kg/day, i.p., post-natal
Acknowledgments
We gratefully thank Professor Dazert for showing his spiral ganglion explant preparation. The authors were funded by KKF (a hospital internal funding organization of the Faculty of Medicine of the Technical University of Munich).
References (29)
Chemical synaptic transmission in the cochlea
Prog. Neurobiol.
(1995)- et al.
Glutamate neurotoxicity in the developing rat cochlea: physiological and morphological approaches
Brain Res.
(1991) - et al.
A role of glutamate in drug-induced ototoxicity: in vivo microdialysis study combined with on-line enzyme fluorometric detection of glutamate in the guinea pig cochlea
Brain Res.
(2000) - et al.
Kanamycin ototoxicity in glutamate transporter knockout mice
Neurosci. Lett.
(2005) - et al.
Efflux of glutamate into the perilymph of the cochlea following transient ischemia in the gerbil
Neurosci. Lett.
(1997) - et al.
Cell death in the inner ear associated with aging is apoptosis?
Brain Res.
(1997) - et al.
Activation of caspase-3 is associated with oxidative stress in the hydropic guinea pig cochlea
Hear. Res.
(2005) - et al.
Interaction of spiral ganglion neuron processes with alloplastic materials in vitro
Hear. Res.
(2002) - et al.
NMDA receptor blockage protects against permanent noise-induced hearing loss but not its potentiation by carbon monoxide
Hear. Res.
(2001) - et al.
Protection of auditory function against noise trauma with local caroverine administration in guinea pigs
Hear. Res.
(2004)
Peripheral and central target-derived trophic factor(s) effects on auditory neurons
Hear. Res.
Calpain inhibitors protect auditory sensory cells from hypoxia and neurotrophin-withdrawal induced apoptosis
Brain Res.
Exacerbation of noise-induced hearing loss in mice lacking the glutamate transporter GLAST
J. Neurosci.
Pathophysiology of the glutamatergic synapses in the cochlea
Acta Otolaryngol. (Stockh)
Cited by (21)
Increased oxidative stress, inflammation, and glutamate: Potential preventive and therapeutic targets for hearing disorders
2020, Mechanisms of Ageing and DevelopmentCitation Excerpt :Exposure to noise, aminoglycoside antibiotics, cochlea ischemia, or trauma caused excessive release of glutamate from the inner hair cells into the synaptic cleft. The high levels of glutamatergic excitation caused swelling and degeneration of the dendrites of spiral ganglion neurons and death of neurons in culture (Steinbach and Lutz, 2007). The studies discussed above show that most ototoxic agents mediate their action by increasing the levels of oxidative stress, chronic inflammation, and glutamate.
Alpha2-adrenergic receptors in spiral ganglion neurons may mediate protective effects of brimonidine and yohimbine against glutamate and hydrogen peroxide toxicity
2013, NeuroscienceCitation Excerpt :The application of glutamate or glutamate agonists results in functional deficits and swelling of auditory neurons equivalent to those observed after noise exposure (Puel et al., 1998; Yamasoba et al., 2005). A study directly shows that apoptosis is induced by the neurotoxic effect of high concentrations of glutamate on neurites and SGNs (Steinbach and Lutz, 2007). It is well known that free radicals, which include reactive oxygen species and reactive nitrogen species, are essential for cellular life processes.
Change in gene expression levels of GABA, glutamate and neurosteroid pathways due to acoustic trauma in the cochlea
2021, Journal of NeurogeneticsAge-Related Hearing Impairment Associated NAT2, GRM7, GRHL2 Susceptibility Gene Polymorphisms and Haplotypes in Roma and Hungarian Populations
2019, Pathology and Oncology ResearchProtection of Spiral Ganglion Neurons and Prevention of Auditory Neuropathy
2019, Advances in Experimental Medicine and Biology