Cocaine-regulated and amphetamine-regulated transcript (CART) is a neuropeptide with reported neuroprotective effects in ischemic cerebral injury. However, its mechanism has not yet been elucidated. Herein, we investigated the role and mechanism of CART in synaptic plasticity in neurons after ischemic cerebral stroke. We found that the survival rate of the oxygen-glucose deprivation (OGD) neurons was increased after CART treatment. Moreover, CART treatment significantly attenuated ischemia-induced neuronal synaptic damage and increased synaptophysin expression. In addition, the number of presynaptic vesicles was increased and the postsynaptic density (PSD) was thickened after CART treatment. Mechanistically, CART treatment enhanced the expression of Arc mRNA in a cAMP response element binding protein (CREB) dependent manner in OGD neurons, and blockade of CREB by KG-501 eliminated the protective effect of CART. Collectively, CART protected the synaptic structure in neurons after ischemic cerebral injury by increasing the Arc expression via upregulating p-CREB.

中文翻译：

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可卡因和苯丙胺调节的转录本保护缺血性脑损伤后神经元的突触结构

可卡因调节和苯丙胺调节的转录物 (CART) 是一种神经肽，据报道在缺血性脑损伤中具有神经保护作用。然而，其机制尚未阐明。在此，我们研究了 CART 在缺血性脑卒中后神经元突触可塑性中的作用和机制。我们发现 CART 治疗后氧-葡萄糖剥夺 (OGD) 神经元的存活率增加。此外，CART 治疗显着减弱了缺血引起的神经元突触损伤并增加了突触素的表达。此外，CART治疗后突触前囊泡数量增加，突触后密度（PSD）增厚。从机制上讲，CART 处理增强了 OGD 神经元中 Arc mRNA 以 cAMP 反应元件结合蛋白 (CREB) 依赖性方式的表达，KG-501 对 CREB ​​的阻断消除了 CART 的保护作用。总的来说，CART 通过上调 p-CREB ​​增加 Arc 表达来保护缺血性脑损伤后神经元的突触结构。