胆碱能和多巴胺能神经元的神经退行性是阿尔茨海默病或帕金森病的主要特征。 钙稳态失调可能是这个过程的一部分，抗钙离子内流可能在两种疾病中具有神经保护性质。 因此，我们研究了L型钙通道（LTCC）抑制剂对大鼠器官otypic vibrosection模型中的胆碱能和多巴胺能神经元的假定神经保护或神经毒性活性。 经过初生日10天的大鼠的冠状或矢状振动切片（200微米厚）在0.4微米半透膜上培养2周，并添加10ng / ml神经生长因子（NGF）和/或胶质细胞衍生的神经营养因子（GDNF）以维持胆碱能或多巴胺能神经元的生存。 然后，将切片与0.1、1或10微米的伊司特丹、尼卡地平或维拉帕米处理2周，以探索细胞毒性。 另外，为了探索神经保护活性，振动切片在没有生长因子的情况下但与伊司特丹或维拉帕米或尼卡地平、尼莫地平或硝苯地平一起孵育4周。 我们的数据表明，所有LTCC抑制剂对胆碱能和多巴胺能神经元都没有神经毒性影响。 此外，LTCC抑制剂对胆碱能神经元也没有任何神经保护作用。 然而，尼莫地平和硝苯地平显著增强了多巴胺能黑质（SN）的存活，但不是腹侧结构区（VTA）神经元，而尼卡地平、伊司特丹和维拉帕米没有影响。 硝苯地平（以及更强的GDNF）降低了炎性细胞因子（巨噬细胞炎性蛋白-2，肿瘤坏死因子-α），但不影响氧化应激或半胱氨酸蛋白酶-3活性，并不干扰铁介导的过载。 我们的数据表明，尼莫地平和硝苯地平极具潜力地增强了轴索切断SN神经元的存活，可能影响炎症过程。 版权所有©2014 Elsevier B.V.。

Neurodegeneration of cholinergic and dopaminergic neurons is a major hallmark in Alzheimer's or Parkinson's disease, respectively. A dysregulation in calcium homeostasis may be part of this process and counteracting calcium influx may have neuroprotective properties in both diseases. Therefore, we investigated the putative neuroprotective or neurotoxic activity of L-type calcium channel (LTCC) inhibitors on cholinergic and dopaminergic neurons in a rat organotypic vibrosection model. Sagittal or coronal vibrosections (200 μm thick) of postnatal day 10 rats were cultured on 0.4 μm semipermeable membranes for 2 weeks with 10 ng/ml nerve growth factor (NGF) and/or glial-cell line derived neurotrophic factor (GDNF) to maintain survival of cholinergic or dopaminergic neurons, respectively. Thereafter, sections were incubated with 0.1, 1 or 10 μM isradipine, nicardipine or verapamil for 2 weeks to explore cytotoxicity. Alternatively, in order to explore neuroprotective activity, vibrosections were incubated without growth factors but with isradipine or verapamil or with nicardipine, nimodipine or nifedipine from the beginning for 4 weeks. Our data show that all LTCC inhibitors exhibited no neurotoxic effect on cholinergic and dopaminergic neurons. Further, LTCC inhibitors did not have any neuroprotective activity on cholinergic neurons. However, nimodipine and nifedipine significantly enhanced the survival of dopaminergic substantia nigra (SN) but not ventral tegmental area (VTA) neurons, while nicardipine, isradipine and verapamil had no effect. Nifedipine (and more potently GDNF) reduced inflammatory cytokines (macrophage inflammatory protein-2, tumor necrosis factor-α), but did not influence oxidative stress or caspase-3 activity and did not interfere with iron-mediated overload. Our data show that nifedipine and nimodipine are very potent to enhance the survival of axotomized SN neurons, possibly influencing inflammatory processes.Copyright © 2014 Elsevier B.V. All rights reserved.