Aspirin selectively augmented N-methyl-d-aspartate types of glutamate responses in cultured spiral ganglion neurons of mice

Peng, Ben-Gang; Chen, Shanping; Lin, Xiaobo

doi:10.1016/s0304-3940(03)00296-9

Cited by 62 publications

(52 citation statements)

References 20 publications

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“…In agreement with the current view that glutamate is the afferent neurotransmitter of hair cells, acting on defined glutamate receptors (Puel, 1995), salicylate was shown recently to potentiate glutamate-mediated currents in cochlear neurons (Peng et al, 2003). This would directly lead to a change in the opening kinetics of voltage-dependent L-type Ca 2ϩ channels.…”

supporting

confidence: 83%

“…A dose-dependent effect of salicylate has been described to act by potentiating NMDA receptor currents in cortical (Vane et al, 1998) or cochlear neurons (Peng et al, 2003). The experimental conditions used may thus act through changes in glutamate or NMDA receptors, which initiate the calcium- Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Salicylate either reduces (Wallhäusser-Franke et al, 2003) or increases neuronal firing rates (Evans and Borerwe, 1982;Wallhäusser-Franke et al, 2003) and exhibits dose-dependent effects (Stypulkowski, 1990). A dose-dependent effect of salicylate has been described to act by potentiating NMDA receptor currents in cortical or spiral ganglion neurons (Peng et al, 2003). Salicylate, however, may also influence cochlear neuron excitability through its inhibitory influence on outer hair cell motility (Grosh et al, 2004), thereby differentially facilitating the excitatory effects of glutamate .…”

mentioning

confidence: 99%

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Salicylate Alters the Expression of Calcium Response Transcription Factor 1 in the Cochlea: Implications for Brain-Derived Neurotrophic Factor Transcriptional Regulation

Singer

Panford-Walsh²,

Watermann³

et al. 2008

Mol Pharmacol

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Brain-derived neurotrophic factor (BDNF) is a key neurotrophin whose expression is altered in response to neurological activity, influencing both short-and long-term synaptic changes. The BDNF gene consists of eight upstream exons (I-VII), each of which has a distinct promoter and can be independently spliced to the ninth coding exon (IX). We showed recently that the expression of BDNF exon IV in the cochlea is altered after exposure to salicylate, an ototoxic drug that in high doses is able to induce hearing loss and tinnitus. These changes were a crucial trigger for plasticity changes in the central auditory system. BDNF exon IV expression is regulated via interaction between calcium-response elements CaRE1, CaRE2, and CaRE3/Cre (CaREs) that are bound by the transcription factors CaRF1, upstream stimulatory factors 1 and 2 (USF1/2), and cAMP/Ca 2ϩ response element-binding protein (CREB), respectively. To determine whether the salicylate-induced changes in cochlear BDNF exon IV expression include a differential use of the CaRE binding proteins, we studied the level of the corresponding binding proteins in the spiral ganglion neurons before and after systemic application of concentrated salicylate using in situ hybridization and RT-PCR. BDNF exon IV and CaRF1 expression were up-regulated after application of salicylate, whereas USF1/2 and CREB mRNA expression remained unaffected. The changes in BDNF exon IV and CaRF1 expression were also dose-dependent. The data show Ca 2ϩ and CaRF1 as messengers of trauma (salicylate)-induced altered BDNF levels in the cochlea. Furthermore, they also provide the first evidence that a differential regulation of BDNF transcription factors might participate in BDNF-mediated plasticity changes.

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supporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Salicylate Alters the Expression of Calcium Response Transcription Factor 1 in the Cochlea: Implications for Brain-Derived Neurotrophic Factor Transcriptional Regulation

Singer

Panford-Walsh²,

Watermann³

et al. 2008

Mol Pharmacol

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“…Glu-induced peak current amplitude and membrane depolarization were considerably increased in the presence of NaSal by enabling NMDA receptor activation. Consistently, Peng et al (2003) reported an aspirin-induced potentiation of NMDA responses on cultured spiral ganglion neurons from young postnatal mice. The main difference between our respective results is that Peng et al (2003) also reported NMDA-mediated responses without aspirin.…”

Section: Salicylate Modulates Nmda Receptor Responsesmentioning

confidence: 58%

Salicylate Enables Cochlear Arachidonic-Acid-Sensitive NMDA Receptor Responses

Ruel¹,

Chabbert²,

Nouvian³

et al. 2008

J. Neurosci.

121

107

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Currently, many millions of people treated for various ailments receive high doses of salicylate. Consequently, understanding the mechanisms by which salicylate induces tinnitus is an important issue for the research community. Behavioral testing in rats have shown that tinnitus induced by salicylate or mefenamate (both cyclooxygenase blockers) are mediated by cochlear NMDA receptors. Here we report that the synapses between the sensory inner hair cells and the dendrites of the cochlear spiral ganglion neurons express NMDA receptors. Patch-clamp recordings and two-photon calcium imaging demonstrated that salicylate and arachidonate (a substrate of cyclooxygenase) enabled the calcium flux and the neural excitatory effects of NMDA on cochlear spiral ganglion neurons. Salicylate also increased the arachidonate content of the whole cochlea in vivo. Single-unit recordings of auditory nerve fibers in adult guinea pig confirmed the neural excitatory effect of salicylate and the blockade of this effect by NMDA antagonist. These results suggest that salicylate inhibits cochlear cyclooxygenase, which increased levels of arachidonate. The increased levels of arachidonate then act on NMDA receptors to enable NMDA responses to glutamate that inner hair cells spontaneously release. This new pharmacological profile of salicylate provides a molecular mechanism for the generation of tinnitus at the periphery of the auditory system.

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“…Recently, salicylate was described to act by potentiating NMDA receptor currents in cortical (Vane et al, 1998) or spiral ganglion neurons in a dose-dependent manner (Peng et al, 2003). A salicylate-induced increase in Ca 2ϩ through NMDA receptors may not only participate in increased BDNF expression but may also alter spontaneous auditory nerve activity (Puel et al, 2002;Muller et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Midazolam Reverses Salicylate-Induced Changes in Brain-Derived Neurotrophic Factor and Arg3.1 Expression: Implications for Tinnitus Perception and Auditory Plasticity

et al. 2008

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Tinnitus is a phantom auditory perception, which can be induced via application of concentrated sodium salicylate, and is known to be associated with hearing loss and altered neuronal excitability in peripheral and central auditory neurons. The molecular features of this excitability, however, has been poorly characterized to date. Brain-derived neurotrophic factor (BDNF), the activity-dependent cytoskeletal protein (Arg3.1, also known as Arc), and c-Fos are known to be affected by changes in excitability and plasticity. Using reverse transcription-polymerase chain reaction, in situ hybridization, and immunohistochemistry, the expression of these genes was monitored in the rat auditory system after local (cochlear) and systemic application of salicylate. Induction of tinnitus and hearing loss was verified in a behavioral model. Regardless of the mode of salicylate application, a common pattern became evident: 1) BDNF mRNA expression was increased in the spiral ganglion neurons of the cochlea; and 2) Arg3.1 expression was significantly reduced in the auditory cortex. Local application of the GABA A receptor modulator midazolam resulted in the reversal not only of salicylate-induced changes in cochlear BDNF expression, but also in cortical Arg3.1 expression, indicating that the tinnitus-associated changes in cochlear BDNF expression trigger the decline of cortical Arg3.1 expression. Furthermore, local midazolam application reduced tinnitus perception in the animal model. These findings support Arg3.1 and BDNF as markers for activity changes in the auditory system and suggest a role of GABAergic inhibition of cochlear neurons in the modulation of Arg3.1 plasticity changes in the auditory cortex and tinnitus perception.

show abstract

Aspirin selectively augmented N-methyl-d-aspartate types of glutamate responses in cultured spiral ganglion neurons of mice

Cited by 62 publications

References 20 publications

Salicylate Alters the Expression of Calcium Response Transcription Factor 1 in the Cochlea: Implications for Brain-Derived Neurotrophic Factor Transcriptional Regulation

Salicylate Alters the Expression of Calcium Response Transcription Factor 1 in the Cochlea: Implications for Brain-Derived Neurotrophic Factor Transcriptional Regulation

Salicylate Enables Cochlear Arachidonic-Acid-Sensitive NMDA Receptor Responses

Midazolam Reverses Salicylate-Induced Changes in Brain-Derived Neurotrophic Factor and Arg3.1 Expression: Implications for Tinnitus Perception and Auditory Plasticity

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