Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
Department of Biomedical Sciences, Neuro-Endocrine-Fluorescence (NEF) Laboratory, University of Cagliari, Italy.
Brain Res. 2021 Dec 15;1773:147705. doi: 10.1016/j.brainres.2021.147705. Epub 2021 Oct 29.
Saporin conjugated to oxytocin (OXY-SAP) destroys neurons expressing oxytocinergic receptors. When injected unilaterally in the substantia nigra of male rats, OXY-SAP causes a dose-dependent decrease up to 55 % in nigral Tyrosine Hydroxylase (TH)-immunoreactivity compared to control mock peptide BLANK-SAP- and PBS-treated rats or the contralateral substantia nigra. TH decrease was parallel to a dopamine content decrease in the ipsilateral striatum compared to BLANK-SAP- or PBS-treated rats or the contralateral striatum. OXY-SAP-treated rats showed a small but significant increase of locomotor activity 28 days after intranigral injection in the Open field test compared to BLANK-SAP- or PBS-treated rats, in line with an inhibitory role of nigral oxytocin on locomotor activity. OXY-SAP-, but not BLANK-SAP- or PBS-treated rats, also showed marked dose-dependent rotational turning ipsilateral to the injected substantia nigra when challenged with d-amphetamine, but not with apomorphine. Under isoflurane anesthesia OXY-SAP-treated rats showed levels of extracellular dopamine in the dialysate from the ipsilateral striatum only half those of BLANK-SAP- or PBS-treated rats or the contralateral striatum. When treated with d-amphetamine, OXY-SAP_60/120 rats showed increased extracellular dopamine levels in the dialysate from the ipsilateral striatum two third/one third only of those found in BLANK-SAP- or PBS-treated rats or the contralateral striatum, respectively. These results show that OXY-SAP destroys nigrostriatal dopaminergic neurons expressing oxytocin receptors leading to a reduced striatal dopamine function.
苏巴肽连接催产素（OXY-SAP）可破坏表达催产素受体的神经元。当将其单侧注射到雄性大鼠的黑质中时，与对照假肽 BLANK-SAP 和 PBS 处理的大鼠或对侧黑质相比，OXY-SAP 会导致黑质酪氨酸羟化酶（TH）免疫反应性降低，剂量依赖性降低 55%。与 BLANK-SAP 或 PBS 处理的大鼠或对侧纹状体相比，TH 减少与同侧纹状体中的多巴胺含量减少平行。与 BLANK-SAP 或 PBS 处理的大鼠相比，OXY-SAP 处理的大鼠在黑质内注射后 28 天的旷场测试中表现出轻微但显著的运动活性增加，这与黑质催产素对运动活性的抑制作用一致。OXY-SAP-，但不是 BLANK-SAP-或 PBS-处理的大鼠，在受到 d-苯丙胺挑战时，也表现出明显的剂量依赖性向注射的黑质侧旋转，而不是阿扑吗啡。在异氟烷麻醉下，OXY-SAP 处理的大鼠在来自对侧纹状体的透析液中的细胞外多巴胺水平仅为 BLANK-SAP 或 PBS 处理的大鼠或对侧纹状体的一半。当用 d-苯丙胺处理时，OXY-SAP_60/120 大鼠在来自对侧纹状体的透析液中的细胞外多巴胺水平增加，仅为 BLANK-SAP 或 PBS 处理的大鼠或对侧纹状体的三分之二/三分之一。这些结果表明，OXY-SAP 破坏了表达催产素受体的黑质纹状体多巴胺能神经元，导致纹状体多巴胺功能降低。
