Discovery Neuroscience, Pfizer Global Research and Development, CN8000, Princeton, NJ 08534, USA.
Neurodegener Dis. 2010;7(1-3):153-9. doi: 10.1159/000289227. Epub 2010 Mar 3.
Parkinson's disease (PD) is a progressive neurodegenerative condition characterized by an increasing loss of dopaminergic neurons resulting in motor dysfunction. However, cognitive impairments in PD patients are a common clinical feature that has gained increased attention.
The purpose of the current study was to evaluate the effects of an MPTP-induced dopaminergic lesion in mice on social odor recognition (SOR) memory.
Mice were acutely treated with MPTP and evaluated for memory impairments in the SOR assay and characterized using biochemical and immunohistochemical methods approximately 2 weeks later.
Here we demonstrate that SOR memory is sensitive to MPTP treatment and that it correlates with multiple measures of nigrostriatal integrity. MPTP treatment of C57BL/6N mice produced a profound decrease in dopamine levels, dopamine transporter binding and tyrosine hydroxylase immunoreactivity in the striatum. These impairments in stratial dopaminergic function were blocked by pretreatment with the MAO-B inhibitor deprenyl. Changes in the dopaminergic system parallel those observed in SOR with MPTP treatment impairing recognition memory in the absence of a deficit in odor discrimination during learning. Deprenyl pretreatment blocked the MPTP-induced impairment of SOR memory.
The use of the SOR memory model may provide a preclinical method for evaluating cognitive therapies for PD.
帕金森病（PD）是一种进行性神经退行性疾病，其特征是多巴胺能神经元逐渐丧失，导致运动功能障碍。然而，PD 患者的认知障碍是一种常见的临床特征，已引起越来越多的关注。
本研究旨在评估 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的小鼠多巴胺能神经元损伤对社交气味识别（SOR）记忆的影响。
急性给予 MPTP 处理小鼠，在 SOR 测定中评估记忆障碍，并在大约 2 周后使用生化和免疫组织化学方法进行特征描述。
我们证明 SOR 记忆对 MPTP 处理敏感，并且与多个黑质纹状体完整性测量相关。MPTP 处理 C57BL/6N 小鼠导致纹状体中的多巴胺水平、多巴胺转运体结合和酪氨酸羟化酶免疫反应性显著降低。纹状体多巴胺能功能的这些损伤被 MAO-B 抑制剂丙炔苯丙胺的预处理所阻断。多巴胺能系统的变化与 SOR 中观察到的变化平行，MPTP 处理损害了识别记忆，而在学习过程中没有气味辨别缺陷。丙炔苯丙胺预处理可阻断 MPTP 诱导的 SOR 记忆损伤。
使用 SOR 记忆模型可能为评估 PD 的认知疗法提供一种临床前方法。
