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Dopamine in the auditory brainstem and midbrain: co-localization with amino acid neurotransmitters and gene expression following cochlear trauma

机译:听觉脑干和中脑中的多巴胺:与耳蜗创伤后氨基酸神经递质共定位和基因表达

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摘要

Dopamine (DA) modulates the effects of amino acid neurotransmitters (AANs), including GABA and glutamate, in motor, visual, olfactory, and reward systems (; ; ). The results suggest that DA may play a similar modulatory role in the auditory pathways. Previous studies have shown that deafness results in decreased GABA release, changes in excitatory neurotransmitter levels, and increased spontaneous neuronal activity within brainstem regions related to auditory function. Modulation of the expression and localization of tyrosine hydroxylase (TH; the rate limiting enzyme in the production of DA) in the IC following cochlear trauma has been previously reported (). In the current study the possibility of co-localization of TH with AANs was examined. Changes in the gene expression of TH were compared with changes in the gene expression of markers for AANs in the cochlear nucleus (CN) and inferior colliculus (IC) to determine whether those deafness related changes occur concurrently. The results indicate that bilateral cochlear ablation significantly reduced TH gene expression in the CN after 2 months while in the IC the reduction in TH was observed at both 3 days and 2 months following ablation. Furthermore, in the CN, glycine transporter 2 (GLYT2) and the GABA transporter (GABAtp) were also significantly reduced only after 2 months. However, in the IC, DA receptor 1 (DRDA1), vesicular glutamate transporters 2 and 3 (VGLUT2, VGLUT3), GABAtp and GAD67 were reduced in expression both at the 3 days and 2 months time points. A close relationship between the distribution of TH and several of the AANs was determined in both the CN and the IC. In addition, GLYT2 and VGLUT3 each co-localized with TH within IC somata and dendrites. Therefore, the results of the current study suggest that DA is spatially well positioned to influence the effects of AANs on auditory neurons.
机译:多巴胺(DA)在运动,视觉,嗅觉和奖励系统中调节包括GABA和谷氨酸在内的氨基酸神经递质(AAN)的作用。结果表明,DA可能在听觉途径中起类似的调节作用。先前的研究表明,耳聋可导致GABA释放减少,兴奋性神经递质水平变化以及与听觉功能相关的脑干区域内的自发神经元活动增加。耳蜗创伤后IC中酪氨酸羟化酶(TH; DA产生的限速酶)的表达和定位的调节已有报道()。在当前的研究中,研究了TH与AAN共同定位的可能性。将TH的基因表达变化与耳蜗核(CN)和下丘脑(IC)中AAN标记的基因表达变化进行比较,以确定与耳聋相关的变化是否同时发生。结果表明,双侧耳蜗消融在2个月后显着降低了CN中TH基因的表达,而在IC中,消融后3天和2个月均观察到TH的降低。此外,在CN中,甘氨酸转运蛋白2(GLYT2)和GABA转运蛋白(GABAtp)也仅在2个月后显着降低。然而,在IC中,DA受体1(DRDA1),囊泡谷氨酸转运蛋白2和3(VGLUT2,VGLUT3),GABAtp和GAD67在3天和2个月时间点均降低了表达。在CN和IC中都确定了TH的分布与几种AAN之间的密切关系。此外,GLYT2和VGLUT3分别与TH在IC体细胞和树突中共定位。因此,本研究的结果表明,DA在空间上处于良好位置,可以影响AAN对听觉神经元的影响。

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