OBJECTIVE Alzheimer's disease (AD) is an age-related devastating neurodegenerative disorder. The hippocampus and cerebral cortex are the most closely related brain regions of cognitive function and neurogenesis. The present study investigated the role of C-terminal-binding protein 1 (CTBP1) in AD. METHODS AD rat models were established through intracerebroventricular injection of β-amyloid polypeptide Aβ(25-35) and intragastric administration of aluminum chloride solution, and the expression pattern that CTBP1 showed in the hippocampus and cerebral cortex was determined. The learning and memory abilities of AD rats after CTBP1 overexpression were assessed. Hippocampal and cortical neurons were transfected with siRNA against CTBP1 or CTBP1-overexpressing plasmids in order to study the effects of CTBP1 elevation or depletion on neuron morphological changes, apoptosis, and viability. The expression of CTBP1, proapoptotic factor (B-cell lymphoma 2; Bcl-2), and antiapoptotic factors (Bcl-2-associated X protein [Bax] and caspase-3) was subsequently evaluated. RESULTS CTBP1 was poorly expressed in the hippocampus and cerebral cortex. AD rats displayed enhanced learning and memory abilities following CTBP1 overexpression. Furthermore, overexpression of CTBP1 improved morphological changes of hippocampal and cortical neurons, increased neuron activity, and inhibited neuron apoptosis in AD rats. Moreover, the expression of Bax and caspase-3 decreased, yet Bcl-2 increased. CONCLUSION Collectively, CTBP1 plays a protective role in the degeneration of hippocampal and cortical neurons whereby overexpressed CTBP1 attenuated the hippocampal and cortical neuron apoptosis and enhanced neuron activity, highlighting the potential of CTBP1 as a target for AD treatment.

中文翻译：

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CTBP1在阿尔茨海默氏病大鼠模型中保护海马和皮层神经元。

目的阿尔茨海默氏病（AD）是一种与年龄有关的破坏性神经退行性疾病。海马和大脑皮层是认知功能和神经发生最密切相关的大脑区域。本研究调查了C末端结合蛋白1（CTBP1）在AD中的作用。方法通过脑室内注射β-淀粉样多肽Aβ（25-35）并胃内注射氯化铝建立AD大鼠模型，并测定CTBP1在海马和大脑皮层的表达模式。评估CTBP1过表达后AD大鼠的学习和记忆能力。为了研究CTBP1升高或耗竭对神经元形态变化，细胞凋亡和生存力的影响，将siRNA转染海马和皮质神经元以对抗CTBP1或CTBP1过表达的质粒。随后评估了CTBP1，促凋亡因子（B细胞淋巴瘤2； Bcl-2）和抗凋亡因子（Bcl-2相关X蛋白[Bax]和caspase-3）的表达。结果CTBP1在海马和大脑皮层中表达较弱。AD大鼠在CTBP1过表达后显示出增强的学习和记忆能力。此外，CTBP1的过表达改善了AD大鼠海马和皮质神经元的形态变化，增加了神经元活性，并抑制了神经元凋亡。此外，Bax和caspase-3的表达减少，而Bcl-2的表达增加。结论集体而言，