Molecular changes associated with the endolymphatic hydrops model
| Autor: | Samantha Anne, Lauren B. Kisley, Cliff A. Megerian, Kumar N. Alagramam, Syed T. Tajuddin, Patrick Leahy |
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| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Amino Acid Transport System X-AG Guinea Pigs Excitotoxicity Glutamic Acid Nitric Oxide Synthase Type I medicine.disease_cause Endolymphatic duct Glutamatergic Glutamate homeostasis Glutamate-Ammonia Ligase Internal medicine medicine Glutamate aspartate transporter Animals Endolymphatic Hydrops RNA Messenger Endolymphatic hydrops biology business.industry Caspase 3 Reverse Transcriptase Polymerase Chain Reaction Neurotoxicity Glutamate receptor Anatomy medicine.disease Sensory Systems Cochlea Up-Regulation Endocrinology medicine.anatomical_structure Otorhinolaryngology biology.protein Female Neurology (clinical) business |
| Zdroj: | Otologyneurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 28(6) |
| ISSN: | 1531-7129 |
| Popis: | HYPOTHESIS Hearing loss and cochlear degeneration in the guinea pig model of endolymphatic hydrops (ELH) results, in part, from toxic levels of excitatory amino acids (EAAs) such as glutamate, which in turn leads to changes in the expression of genes linked to intracellular glutamate homeostasis and apoptosis, leading to neuronal cell death. BACKGROUND EAAs have been shown to play a role in normal auditory signal transmission in mammalian cochlea, but have also been implicated in neurotoxicity when levels are elevated. Changes in the expression of specific genes involved in the glutamatergic and apoptotic pathway would serve as evidence for excitotoxicity linked to elevated levels of glutamate. METHODS Guinea pigs underwent surgical obliteration of the endolymphatic duct, and then a timed harvest of the treated (right) and control (left) cochlea and subsequent quantification of gene expression via real-time quantitative polymerase chain reaction. RESULTS Quantitative polymerase chain reaction data show significant upregulation of glutamate aspartate transporter and neuronal nitric oxide synthase mRNA levels 3 weeks postsurgery and Caspase 3 mRNA levels 1 week postsurgery. No significant changes were detected in glutamine synthetase expression levels. CONCLUSION Upregulation of genes involved in glutamate homeostasis and the apoptotic pathway in animals treated with endolymphatic duct obstruction (usually associated with secondary ELH) support the hypothesis that EAAs may play a role in the pathophysiology of ELH-related cochlear injury. Inhibitors to these pathways can be useful for the study of new avenues to delay or prevent ELH-related hearing loss. |
| Databáze: | OpenAIRE |
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