NADPH Oxidase 2-Mediated Insult in the Auditory Cortex of Zucker Diabetic Fatty Rats
Clinical data has confirmed that auditory impairment may be a secondary symptom of type 2 diabetes mellitus (T2DM). However, mechanisms underlying pathologic changes that occur in the auditory system, especially in the central auditory system (CAS), remain poorly understood. In this study, Zucker di...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2019/3591605 |
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| author | Zheng-De Du Wei Wei Shukui Yu Qing-Ling Song Ke Liu Shu-Sheng Gong |
| author_facet | Zheng-De Du Wei Wei Shukui Yu Qing-Ling Song Ke Liu Shu-Sheng Gong |
| author_sort | Zheng-De Du |
| collection | DOAJ |
| description | Clinical data has confirmed that auditory impairment may be a secondary symptom of type 2 diabetes mellitus (T2DM). However, mechanisms underlying pathologic changes that occur in the auditory system, especially in the central auditory system (CAS), remain poorly understood. In this study, Zucker diabetic fatty (ZDF) rats were used as a T2DM rat model to observe ultrastructural alterations in the auditory cortex and investigate possible mechanisms underlying CAS damage in T2DM. The auditory brainstem response (ABR) of ZDF rats was found to be markedly elevated in low (8 kHz) and high (32 kHz) frequencies. Protein expression of NADPH oxidase 2 (NOX2) and its matching subunits P22phox, P47phox, and P67phox was increased in the auditory cortex of ZDF rats. Expression of 8-hydroxy-2-deoxyguanosine (8-OHdG), a marker of DNA oxidative damage, was also increased in the neuronal mitochondria of the auditory cortex of ZDF rats. Additionally, decreases in the mitochondrial total antioxidant capabilities (T-AOC), adenosine triphosphate (ATP) production, and mitochondrial membrane potential (MMP) were detected in the auditory cortex of ZDF rats, suggesting mitochondrial dysfunction. Transmission electron microscopy results indicated that ultrastructural damage had occurred to neurovascular units and mitochondria in the auditory cortex of ZDF rats. Furthermore, cytochrome c (Cyt c) translocation from mitochondria to cytoplasm and caspase 3-dependent apoptosis were also detected in the auditory cortex of ZDF rats. Consequently, the study demonstrated that T2DM may cause morphological damage to the CAS and that NOX2-associated mitochondrial oxidative damage and apoptosis may be partly responsible for this insult. |
| format | Article |
| id | doaj-art-2f9d871706c842148a664ed0226e3be1 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-2f9d871706c842148a664ed0226e3be12025-02-03T05:46:59ZengWileyNeural Plasticity2090-59041687-54432019-01-01201910.1155/2019/35916053591605NADPH Oxidase 2-Mediated Insult in the Auditory Cortex of Zucker Diabetic Fatty RatsZheng-De Du0Wei Wei1Shukui Yu2Qing-Ling Song3Ke Liu4Shu-Sheng Gong5Department of Otorhinolaryngology, Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xicheng District, Beijing 100050, ChinaDepartment of Otology, Shengjing Hospital, China Medical University, 36 Sanhao Street, Heping District, Shenyang 110004, ChinaDepartment of Otorhinolaryngology, Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xicheng District, Beijing 100050, ChinaDepartment of Otorhinolaryngology, 731 Hospital, China Aerospace Science and Industry Company, No. 3 Courtyard, Gangnanli, Yungang Town, Fengtai District, Beijing 100074, ChinaDepartment of Otorhinolaryngology, Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xicheng District, Beijing 100050, ChinaDepartment of Otorhinolaryngology, Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xicheng District, Beijing 100050, ChinaClinical data has confirmed that auditory impairment may be a secondary symptom of type 2 diabetes mellitus (T2DM). However, mechanisms underlying pathologic changes that occur in the auditory system, especially in the central auditory system (CAS), remain poorly understood. In this study, Zucker diabetic fatty (ZDF) rats were used as a T2DM rat model to observe ultrastructural alterations in the auditory cortex and investigate possible mechanisms underlying CAS damage in T2DM. The auditory brainstem response (ABR) of ZDF rats was found to be markedly elevated in low (8 kHz) and high (32 kHz) frequencies. Protein expression of NADPH oxidase 2 (NOX2) and its matching subunits P22phox, P47phox, and P67phox was increased in the auditory cortex of ZDF rats. Expression of 8-hydroxy-2-deoxyguanosine (8-OHdG), a marker of DNA oxidative damage, was also increased in the neuronal mitochondria of the auditory cortex of ZDF rats. Additionally, decreases in the mitochondrial total antioxidant capabilities (T-AOC), adenosine triphosphate (ATP) production, and mitochondrial membrane potential (MMP) were detected in the auditory cortex of ZDF rats, suggesting mitochondrial dysfunction. Transmission electron microscopy results indicated that ultrastructural damage had occurred to neurovascular units and mitochondria in the auditory cortex of ZDF rats. Furthermore, cytochrome c (Cyt c) translocation from mitochondria to cytoplasm and caspase 3-dependent apoptosis were also detected in the auditory cortex of ZDF rats. Consequently, the study demonstrated that T2DM may cause morphological damage to the CAS and that NOX2-associated mitochondrial oxidative damage and apoptosis may be partly responsible for this insult.http://dx.doi.org/10.1155/2019/3591605 |
| spellingShingle | Zheng-De Du Wei Wei Shukui Yu Qing-Ling Song Ke Liu Shu-Sheng Gong NADPH Oxidase 2-Mediated Insult in the Auditory Cortex of Zucker Diabetic Fatty Rats Neural Plasticity |
| title | NADPH Oxidase 2-Mediated Insult in the Auditory Cortex of Zucker Diabetic Fatty Rats |
| title_full | NADPH Oxidase 2-Mediated Insult in the Auditory Cortex of Zucker Diabetic Fatty Rats |
| title_fullStr | NADPH Oxidase 2-Mediated Insult in the Auditory Cortex of Zucker Diabetic Fatty Rats |
| title_full_unstemmed | NADPH Oxidase 2-Mediated Insult in the Auditory Cortex of Zucker Diabetic Fatty Rats |
| title_short | NADPH Oxidase 2-Mediated Insult in the Auditory Cortex of Zucker Diabetic Fatty Rats |
| title_sort | nadph oxidase 2 mediated insult in the auditory cortex of zucker diabetic fatty rats |
| url | http://dx.doi.org/10.1155/2019/3591605 |
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