El Samad Ali, Jaffal Julia, Ibrahim Dalia R, Schwarz Karin, Schmitz Frank
Institute of Anatomy, Department of Neuroanatomy, Medical School Homburg, Saarland University, 66421 Homburg, Germany.
Biomedicines. 2024 Nov 7;12(11):2545. doi: 10.3390/biomedicines12112545.
Multiple sclerosis is a frequent neuroinflammatory and neurodegenerative disease of the central nervous system that includes alterations in the white and gray matter of the brain. The visual system is frequently affected in multiple sclerosis. Glutamate excitotoxicity might play a role in disease pathogenesis.
In the present study, we analyzed with qualitative and quantitative immunofluorescence microscopy and Western blot analyses whether alterations in the EAAT5 (SLC1A7) glutamate transporter could be involved in the previously observed alterations in structure and function of glutamatergic photoreceptor ribbon synapses in the EAE mouse model of MS. EAAT5 is a presynaptic glutamate transporter located near the presynaptic release sites.
We found that EAAT5 was strongly reduced at the photoreceptor synapses of EAE retinas in comparison to the photoreceptor synapses of the respective control retinas as early as day 9 post-immunization. The Western blot analyses demonstrated a decreased EAAT5 expression in EAE retinas.
Our data illustrate early alterations of the EAAT5 glutamate transporter in the early pre-clinical phase of EAE/MS and suggest an involvement of EAAT5 in the previously observed early synaptic changes at photoreceptor synapses. The precise mechanisms need to be elucidated by future investigations.
多发性硬化症是一种常见的中枢神经系统神经炎症性和神经退行性疾病，包括大脑白质和灰质的改变。视觉系统在多发性硬化症中经常受到影响。谷氨酸兴奋性毒性可能在疾病发病机制中起作用。
在本研究中，我们通过定性和定量免疫荧光显微镜及蛋白质印迹分析，分析了EAAT5（溶质载体家族1成员7）谷氨酸转运体的改变是否可能与先前在多发性硬化症实验性自身免疫性脑脊髓炎（EAE）小鼠模型中观察到的谷氨酸能光感受器带状突触的结构和功能改变有关。EAAT5是一种位于突触前释放位点附近的突触前谷氨酸转运体。
我们发现，早在免疫后第9天，与相应对照视网膜的光感受器突触相比，EAE视网膜的光感受器突触处的EAAT5就大幅减少。蛋白质印迹分析表明EAE视网膜中EAAT5表达降低。
我们的数据说明了EAE/MS临床前期早期EAAT5谷氨酸转运体的改变，并表明EAAT5参与了先前观察到的光感受器突触早期突触变化。确切机制有待未来研究阐明。
