Degeneration of the locus coeruleus (LC), the main source of cerebral noradrenaline (NA), has been reported in diverse neurodegenerative diseases, including Parkinson’s diseases (PD). There is increasing evidence indicating the role of NA deficiency in the prefrontal cortex (PFC) and the development of early cognitive impairments in PD. Here, we evaluated whether a selective noradrenergic lesion of LC caused by 6-hydroxydopamine (6-OHDA) may induce memory deficits and neurochemical alterations in the PFC. Adult male Wistar rats received stereotaxic bilateral injections of 6-OHDA (5 μg/2 μl) into the LC, and two stainless-steel guide cannulas were implanted in the PFC. The SHAM group received just vehicle. To induce a selective noradrenergic lesion, animals received nomifensine (10 mg/kg), a dopamine transporter blocker, one hour before surgery. 6-OHDA-lesioned rats displayed impairments of the short- and long-term object recognition memory associated to reduced content of tyrosine hydroxylase in the LC. Neurochemical analysis revealed an altered mitochondrial membrane potential in LC. Regarding the PFC, an increased ROS production, cell membrane damage, and mitochondrial membrane potential disruption were observed. Remarkably, bilateral NA (1 μg/0.2 μl) infusion into the PFC restored the recognition memory deficits in LC-lesioned rats. These findings indicate that a selective noradrenergic LC lesion induced by 6-OHDA deregulates a noradrenergic network in the PFC, which could be involved in the early memory impairments observed in nondemented PD patients.

中文翻译：

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前额叶皮层对6-OHDA诱导的蓝斑蓝斑病变大鼠认知记忆缺陷的作用。

所述的变性蓝斑（LC），去甲肾上腺素脑的主要来源（NA），已报道在多种神经变性疾病，包括帕金森氏病（PD）。越来越多的证据表明NA缺乏在前额叶皮层（PFC）中的作用以及PD早期认知障碍的发展。在这里，我们评估了由6-羟基多巴胺（6-OHDA）引起的LC选择性去甲肾上腺素能病变是否可能诱发PFC中的记忆缺陷和神经化学改变。成年雄性Wistar大鼠接受6-OHDA（5立体定位双侧注射 μ克/ 2  μl）进入LC，并在PFC中植入了两个不锈钢导管。SHAM小组仅收到车辆。为了诱发选择性的去甲肾上腺素能病变，动物在手术前一小时接受了多巴胺转运蛋白阻滞剂诺米芬（10 mg / kg）。患6-OHDA的大鼠表现出与LC中酪氨酸羟化酶含量降低有关的短期和长期对象识别记忆障碍。神经化学分析显示LC中线粒体膜电位改变。关于PFC，观察到ROS产生增加，细胞膜损伤和线粒体膜电位破坏。值得注意的是，双边NA（1  μ克/ 0.2  μl）输注PFC可以恢复LC病变大鼠的识别记忆障碍。这些发现表明6-OHDA诱发的选择性去甲肾上腺素LC病变使PFC中的去甲肾上腺素网络失调，这可能与未痴呆的PD患者观察到的早期记忆障碍有关。