Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, 84049-900, Brazil.
Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, 84049-900, Brazil.
Neurotox Res. 2018 Nov;34(4):808-819. doi: 10.1007/s12640-018-9912-4. Epub 2018 May 28.
Depression is a highly prevalent and debilitating non-motor symptom observed during the early stages of Parkinson's disease (PD). Although PD prevalence is higher in men, the depressive symptoms in PD are more common in women. Therefore, the aim of this study was to investigate the development of anhedonic- and depressive-like behaviors in male and female mice and the potential mechanisms related to depressive symptoms in an experimental model of PD. Young adult male and female C57BL/6 mice (3 months old) received a single intranasal (i.n.) administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and were submitted to a battery of behavioral tasks (sucrose consumption, splash test, tail suspension, forced swimming and open field tests) to assess their emotional and motor profiles. Considering the role of sexual hormones in emotional behaviors, the same protocol of i.n. MPTP administration and the splash, tail suspension, and open field tests were conducted in ovariectomized (OVX) and aged C57BL/6 female (20 months old) mice. We also investigated the immunocontent of neurotrophins (BDNF, GDNF, and VEGF) in the hippocampus and prefrontal cortex by western blot. I.n. MPTP administration induced more pronounced anhedonic- and selective depressive-like behaviors in female adult mice, also observed in OVX and aged female mice, with the absence of motor impairments. Furthermore, MPTP induced a more pronounced depletion of neurotrophins in the prefrontal cortex and hippocampus in female than male mice. This study provides new evidence of increased susceptibility of female mice to anhedonic- and depressive-like behaviors following i.n. MPTP administration. The observed gender-related effects of MPTP on emotional parameters seem to be linked to increased depletion of neurotrophins (particularly BDNF and GDNF) in the hippocampus and prefrontal cortex of female mice.
抑郁是帕金森病（PD）早期观察到的一种高度普遍且使人虚弱的非运动症状。尽管 PD 的患病率在男性中更高，但 PD 中的抑郁症状在女性中更为常见。因此，本研究旨在研究雄性和雌性小鼠的快感缺失和抑郁样行为的发展，以及 PD 实验模型中与抑郁症状相关的潜在机制。年轻成年雄性和雌性 C57BL/6 小鼠（3 个月大）接受单次鼻腔内（i.n.）给予 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP），并进行一系列行为任务（蔗糖消耗、飞溅测试、悬尾、强迫游泳和旷场测试），以评估它们的情绪和运动概况。考虑到性激素在情绪行为中的作用，相同的 i.n. MPTP 给药方案以及飞溅、悬尾和旷场测试在去卵巢（OVX）和老年 C57BL/6 雌性（20 个月大）小鼠中进行。我们还通过 Western blot 研究了海马体和前额叶皮层中的神经营养因子（BDNF、GDNF 和 VEGF）的免疫含量。i.n. MPTP 给药导致成年雌性小鼠出现更明显的快感缺失和选择性抑郁样行为，在 OVX 和老年雌性小鼠中也观察到这种行为，而没有运动损伤。此外，MPTP 诱导雌性小鼠前额叶皮层和海马体中的神经营养因子（特别是 BDNF 和 GDNF）耗竭更为明显。本研究提供了新的证据，表明鼻腔内给予 MPTP 后，雌性小鼠对快感缺失和抑郁样行为的易感性增加。观察到的 MPTP 对情绪参数的性别相关影响似乎与雌性小鼠海马体和前额叶皮层中神经营养因子（特别是 BDNF 和 GDNF）的耗竭增加有关。
