Dystrophin deficiency caused by mutations of the related gene leads to muscle wasting in Duchenne muscular dystrophy (DMD). Some patients with DMD also present with intellectual disability and various degrees of neurological disorders, which have been related to a decreased number of postsynaptic gamma-aminobutyric acid type A receptors (GABA_ARs) in the hippocampus (HPC) and cerebellum (CBL). The aim of this study was to examine the relevance of dystrophin in the presynaptic GABAergic function in brain regions in which this protein is normally abundant. [³H]-GABA release, induced by nicotinic receptor (nAChR) activation or K⁺ depolarization, and [³H]-GABA uptake were determined using synaptosomes extracted from the cortex (CTX), HPC, and CBL of littermate control and mdx mice. Superfusion of the synaptosomes with nicotine or high K⁺ solutions led to a concentration-dependent and Ca²⁺-dependent [³H]-GABA release in control and mdx synaptosomes. [³H]-GABA release induced by 10 μM nicotine in mdx CBL synaptosomes was 47% less than that in control mice. K⁺-induced [³H]-GABA release did not differ between control and mdx synaptosomes. α7-containing and β2-containing nAChRs were involved in nicotine-induced [³H]-GABA release in control and mdx synaptosomes. Kinetic analysis of [³H]-GABA uptake in mdx CBL synaptosomes showed a reduced (50%) half-maximal uptake time (t_1/2) and increased (44%) rate of [³H]-GABA uptake (V_max) compared to controls. The apparent transporter affinity (K_m) for GABA was not altered. Our findings show that dystrophin deficiency in mdx mice is associated with significant changes in the release and uptake of GABA in the CBL. These presynaptic alterations may be related to the reported decrease in postsynaptic GABA_AR in the same brain region. The results indicate possible dysfunction of GABAergic synapses associated with dystrophin deficiency in the CBL, which may contribute to the cognitive and neurobehavioral disorders in mdx mice and patients with DMD.

由相关基因突变引起的肌营养不良蛋白缺乏会导致杜兴氏肌营养不良症（DMD）的肌肉萎缩。一些DMD患者还表现出智力残疾和各种程度的神经系统疾病，这与海马（HPC）和小脑（CBL）的突触后γ-氨基丁酸_A型受体（GABA _A Rs）数量减少有关。这项研究的目的是检查肌营养不良蛋白与通常富含这种蛋白的大脑区域中突触前GABA能功能的相关性。[ ³ H] -GABA的释放，是由烟碱样受体（nAChR）激活或K ⁺去极化引起的，而[ ³使用从同窝对照和mdx小鼠的皮质（CTX），HPC和CBL中提取的突触小体来确定H] -GABA的摄取。突触小体与尼古丁或高K ⁺溶液的过度融合导致对照和mdx突触小体中浓度依赖性和Ca ²⁺依赖性[ ³ H] -GABA释放。mdx CBL突触体中10μM烟碱诱导的[ ³ H] -GABA释放比对照组小鼠低47％。K ⁺诱导的[ ³ H] -GABA释放在对照和mdx突触小体之间没有差异。含α7和含β2的nAChR参与尼古丁诱导的[ ³H] -GABA在对照和mdx突触小体中释放。在mdx CBL突触体中摄取[ ³ H] -GABA的动力学分析表明，半衰期最长摄取时间（t _1/2）减少（50％），[ ³ H] -GABA摄取（V _max）的比率增加（44％））与对照相比。对GABA的表观转运蛋白亲和力（K _m）没有改变。我们的发现表明，mdx小鼠中的肌营养不良蛋白缺乏症与CBL中GABA的释放和摄取的显着变化有关。这些突触前改变可能与所报道的突触后GABA _A减少有关R在相同的大脑区域。结果表明，与CBL中的肌营养不良蛋白缺乏症相关的GABA能突触可能功能障碍，这可能是mdx小鼠和DMD患者的认知和神经行为障碍的原因。