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对有噪声性耳鸣行为证据的大鼠的背侧耳蜗核中GABA R-α1阳性细胞进行鉴定和定量分析。

Identification and quantification of GABA R-α1-positive cells in the DCN of rats with behavioral evidence of noise-induced tinnitus.

作者信息

Du Xiaoping, Lu Jianzhong, Yokell Zachary, Cheng Weihua, Nakmali Don, Kopke Richard D, West Matthew B

机构信息

Hough Ear Institute, Oklahoma City, OK, United States.

出版信息

IBRO Neurosci Rep. 2025 Jul 16;19:332-344. doi: 10.1016/j.ibneur.2025.07.005. eCollection 2025 Dec.

Abstract

Tinnitus, the perception of a phantom sound, often occurs as a clinical sequela of auditory traumas. However, the underlying mechanisms of tinnitus are largely unknown. In our previous studies, we found more gamma-aminobutyric acid A receptor alpha 1 subunit (GABAR-α1)-positive cells in the dorsal cochlear nucleus (DCN) after noise exposure, however, we were not able to identify the specific types of DCN cells that up-regulated GABAR-α1 after the insult. In the current study, we used Nissl staining, Purkinje cell protein 4 (PCP4) and glutamic acid decarboxylase 67 (GAD67) immunolabeling to identify GABAR-α1-positive cells in the DCN. Each type of GABAR-α1-positive cells was quantified and statistically analyzed using immunostaining and Nissl staining according to their morphology, size and location in the DCN. GABAR-α1-positive cartwheel cells, Golgi cells, as well as ML-stellate and vertical cells were confirmed by dual immunolabeling. In the DCN, the most common GABAR-α1-positive cells were Golgi cells followed by vertical cells and cartwheel cells while very few other cells were GABAR-α1-positive in all conditions. We found significantly more GABAR-α1-positive Golgi cells in the DCN of noise-exposed rats without behavioral evidence of tinnitus compared to normal controls and noise-exposed rats with behavioral evidence of tinnitus. This heightened "context-dependent" inhibition may help to maintain a balanced neuronal network, preventing the potential for tinnitus-related hyperactivity in the auditory pathways.

摘要

耳鸣,即对幻听的感知,常作为听觉创伤的临床后遗症出现。然而,耳鸣的潜在机制在很大程度上尚不清楚。在我们之前的研究中,我们发现噪声暴露后,蜗背侧核(DCN)中γ-氨基丁酸A受体α1亚基(GABAR-α1)阳性细胞增多,然而,我们无法确定在损伤后上调GABAR-α1的DCN细胞的具体类型。在本研究中,我们使用尼氏染色、浦肯野细胞蛋白4(PCP4)和谷氨酸脱羧酶67(GAD67)免疫标记来识别DCN中的GABAR-α1阳性细胞。根据GABAR-α1阳性细胞在DCN中的形态、大小和位置,利用免疫染色和尼氏染色对每种类型的细胞进行定量和统计分析。通过双重免疫标记证实了GABAR-α1阳性的车轮状细胞、高尔基细胞以及ML-星状细胞和垂直细胞。在DCN中,最常见的GABAR-α1阳性细胞是高尔基细胞,其次是垂直细胞和车轮状细胞,而在所有条件下,很少有其他细胞是GABAR-α1阳性的。我们发现,与正常对照组和有耳鸣行为证据的噪声暴露大鼠相比,没有耳鸣行为证据的噪声暴露大鼠的DCN中GABAR-α1阳性高尔基细胞显著更多。这种增强的“情境依赖性”抑制可能有助于维持平衡的神经网络,防止听觉通路中出现与耳鸣相关的过度活动。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15e3/12336005/dfe45a21a760/gr1.jpg

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