Department of Neurology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, China.
Department of Medical Imaging, Shandong Provincial Hospital, Jinan, Shandong 250014, China.
Chin Med J (Engl). 2017 Oct 5;130(19):2302-2306. doi: 10.4103/0366-6999.215336.
Olfactory disorder is an early manifestation of Parkinson's disease (PD), likely to be associated with abnormalities of the dopaminergic neurons in the olfactory bulb (OB); however, the causes of olfactory disorder in PD are not entirely clear. Some studies showed that melatonin (MT) and androgens (mainly testosterone, T) might participate in the pathogenesis of PD. The research aimed to investigate effects of MT or T deficiency on OB dopaminergic neurons in rats.
One hundred and twenty normal male Wistar rats were randomly divided into the control, sham operation pinealectomy (PX), sham operation gonadectomy (GDX), PX, GDX, and PX + GDX groups. After 60 days, glial cell hyperplasia and neuronal apoptosis were examined with hematoxylin and eosin and the TUNEL method; the expression levels of tyrosine hydroxylase (TH), Bax, and Bcl-2 were measured using immunohistochemistry (IH) by the streptavidin peroxidase conjugated method. Comparison among multiple sets used analysis of variance and LSD method or Kruskal-Wallis test and Nemenyi method.
There were no significant differences between the sham operation groups and the control group; thus, they were merged into Group A. There was no significant glial cell hyperplasia (P > 0.05) or change in shape in any of the groups after PX or GDX. The number of apoptotic cells in Groups A (1.41 ± 0.56), PX (12.31 ± 4.68), GDX (20.52 ± 5.13), and PX + GDX (30.23 ± 5.25) successively significantly increased (P < 0.05). The number of TH (+) cells in Groups A (42.62 ± 5.63), PX (37.31 ± 4.32), GDX (31.07 ± 4.21), and PX + GDX (25.22 ± 3.66) was successively significantly decreased (P < 0.05). The gray value of TH (+) cells and fibers in Groups A (98.51 ± 10.36), PX (108.96 ± 13.01), GDX (119.02 ± 12.98), and PX + GDX (128.99 ± 13.39) was successively significantly increased (P < 0.05). The results of Bax staining were as follows: Group A+, Group PX++, Group GDX++, and Group PX+ GDX+++, the results of Bcl-2 in all groups were +.
PX or GDX could lead to OB neurotoxicity in the following groups of rats in the following order: PX < GDX < PX + GDX. PX or GDX increased the ratio of Bax/Bcl-2. The effect of PX and GDX was equal, but both were less than that of PX + GDX. Neurotoxicity as a result of PX or GDX was not related to inflammation.
嗅觉障碍是帕金森病（PD）的早期表现，可能与嗅球（OB）中的多巴胺能神经元异常有关；然而，PD 中嗅觉障碍的原因尚不完全清楚。一些研究表明，褪黑素（MT）和雄激素（主要是睾酮，T）可能参与 PD 的发病机制。本研究旨在探讨 MT 或 T 缺乏对大鼠 OB 多巴胺能神经元的影响。
将 120 只正常雄性 Wistar 大鼠随机分为对照组、假手术去松果体（PX）组、假手术去睾丸（GDX）组、PX 组、GDX 组和 PX+GDX 组。60 天后，采用苏木精-伊红（HE）和 TUNEL 法检测胶质细胞增生和神经元凋亡；采用免疫组织化学（IH）法，通过链霉亲和素过氧化物酶连接法检测酪氨酸羟化酶（TH）、Bax 和 Bcl-2 的表达水平。多组间比较采用方差分析和 LSD 法或 Kruskal-Wallis 检验和 Nemenyi 法。
假手术组与对照组比较无显著性差异，故合并为 A 组。PX 或 GDX 后各组均未见明显的胶质细胞增生（P>0.05）或形态改变。A 组（1.41±0.56）、PX 组（12.31±4.68）、GDX 组（20.52±5.13）和 PX+GDX 组（30.23±5.25）的凋亡细胞数依次明显增加（P<0.05）。A 组（42.62±5.63）、PX 组（37.31±4.32）、GDX 组（31.07±4.21）和 PX+GDX 组（25.22±3.66）TH（+）细胞数依次明显减少（P<0.05）。A 组（98.51±10.36）、PX 组（108.96±13.01）、GDX 组（119.02±12.98）和 PX+GDX 组（128.99±13.39）TH（+）细胞和纤维的灰度值依次明显增加（P<0.05）。Bax 染色结果如下：A 组+，PX 组++，GDX 组+++，各组 Bcl-2 结果均为+。
PX 或 GDX 可导致以下各组大鼠 OB 神经毒性，顺序为：PX<GDX<PX+GDX。PX 或 GDX 增加了 Bax/Bcl-2 的比值。PX 和 GDX 的作用相等，但均小于 PX+GDX。PX 或 GDX 引起的神经毒性与炎症无关。
