Banafshe Hamid Reza, Mohsenpour Mohsen, Ardjmand Abolfazl
Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran.
Department of Pharmacology, Kashan University of Medical Sciences, Kashan, Iran.
Galen Med J. 2018 Aug 11;7:e1044. doi: 10.22086/gmj.v0i0.1044. eCollection 2018.
Protein phosphatase-2B or calcineurin (CN) is the main phosphatase and a critical regulator of cellular pathways for learning, memory, and plasticity. Cyclosporine A(CyA), a phosphatase and peptidyl-prolyl cis/trans isomerase inhibitor, is a common immune suppressant extensively used in tissue transplantation. To further clarify the role of CN in different stages of learning and memory, the aim of the present study was to evaluate the role of CyA in an inhibitory avoidance (IA) model in mice.
Using intracerebroventricular (ICV) injection of different doses of CyA (0.5, 5, and 50 nM) at different periods (pre-/post-training and pre-test), the effect of the drug was evaluated in a step-down IA paradigm. The latency of step-down (sec) was considered a criterion for memory performance.
The pre-training injections of CyA (0.5, 5 nM), however not of 50 nM, impaired IA learning acquisition. The post-training injection of high-dose CyA (50 nM) impaired memory consolidation. The pre-test ICV CyA injection did not impair memory retrieval; the ICV injection of CyA caused no change in locomotion.
These findings suggest that CyA selectively interferes with acquisition, retention, but not retrieval, of information processing in mice. Given the crucial role of CN in common signaling pathway of memory performance and cognition, it could be a probable therapeutic target in the treatment of a wide variety of neurological conditions involving memory.
蛋白磷酸酶2B或钙调神经磷酸酶（CN）是主要的磷酸酶，是学习、记忆和可塑性细胞通路的关键调节因子。环孢素A（CyA）是一种磷酸酶和肽基脯氨酰顺/反异构酶抑制剂，是广泛用于组织移植的常见免疫抑制剂。为了进一步阐明CN在学习和记忆不同阶段的作用，本研究旨在评估CyA在小鼠抑制性回避（IA）模型中的作用。
在不同时期（训练前/后和测试前）通过脑室内（ICV）注射不同剂量的CyA（0.5、5和50 nM），在一步下降IA范式中评估药物的作用。下降潜伏期（秒）被视为记忆表现的标准。
训练前注射CyA（0.5、5 nM），而非50 nM，损害了IA学习获得。训练后注射高剂量CyA（50 nM）损害了记忆巩固。测试前ICV注射CyA未损害记忆检索；ICV注射CyA对运动无影响。
这些发现表明，CyA选择性地干扰小鼠信息处理的获得、保持，但不干扰检索。鉴于CN在记忆表现和认知的共同信号通路中的关键作用，它可能是治疗多种涉及记忆的神经疾病的潜在治疗靶点。
