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嗅觉障碍如何导致抑郁?缰核退化的作用。

How olfaction disorders can cause depression? The role of habenular degeneration.

机构信息

Department of Psychiatry, Medical Faculty, University of Atatürk, Erzurum, Turkey.

出版信息

Neuroscience. 2013 Jun 14;240:63-9. doi: 10.1016/j.neuroscience.2013.02.026. Epub 2013 Feb 26.

DOI:10.1016/j.neuroscience.2013.02.026
PMID:23485804
Abstract

The removal of bilateral olfactory bulbs (OBs) can result in serious behavioral, neurochemical, neuroendocrine, and neuroimmune alterations in depressed patients. However, there is little information on how olfactory bulbectomy (OBX) leads to depression. Habenular nuclei and their connections are important in the regulation of psychomotor and psychosocial behaviors through afferent impulses of the olfactory system. Therefore, we investigated whether OB lesions lead to habenular degeneration. We used a sample of 50 rats (25 female and 25 male) for this study. Of these rats, five male and five female rats were taken as the control group. The remaining 40 rats (20 male and 20 female rats) constituted the study group, and frontal burr holes were performed at the OB level on these rats. OB cauterization was applied to 10 male and 10 female rats (n=10, 10; study group 1), mechanical OBX was applied to five male and five female rats (n=5, 5; study group 2), and no procedure was performed on the remaining 10 rats (n=5, 5). The psychomotor movements; pregnancy rates; and sexual, feeding, maternal, social, and grooming behaviors for both study groups were observed daily for 3 months. Their OBs, olfactory cortices, and habenular complexes were examined using stereological methods. All of the animals in the study groups, especially in the cauterization group, demonstrated anorexia, nutritional disorders, weight loss, psychomotor retardation, sexual aversion, decreased grooming behavior, and reduced social interaction similar to depression symptoms. As compared to the control group, the pregnancy rates, number of offspring per mother rat, and birth weights in the study groups were lower, whereas the number of stillbirths was higher. Gross anatomical examinations revealed that the OBs of all of the animals in the study groups were atrophied. Histopathological examinations detected prominent neuronal loss due to apoptosis in the habenular structures in the study groups. We detected a relationship between a decreased healthy neuronal density of the habenula and depressive symptomatology in rats with OBX. We suggest that olfaction disorders might cause neuropsychiatric disorders by affecting neuronal degeneration in habenular nuclei.

摘要

双侧嗅球(OB)切除可导致抑郁患者出现严重的行为、神经化学、神经内分泌和神经免疫改变。然而,关于嗅球切除术(OBX)如何导致抑郁的信息却很少。缰核及其连接通过嗅觉系统的传入冲动在调节精神运动和心理社会行为方面起着重要作用。因此,我们研究了 OB 损伤是否会导致缰核退化。我们使用了 50 只大鼠(25 只雌性和 25 只雄性)作为研究对象。其中 5 只雄性和 5 只雌性大鼠作为对照组。其余 40 只大鼠(20 只雄性和 20 只雌性大鼠)构成研究组,这些大鼠的 OB 水平进行额骨钻孔。10 只雄性和 10 只雌性大鼠(n=10,10;研究组 1)行 OB 烧灼,5 只雄性和 5 只雌性大鼠(n=5,5;研究组 2)行机械性 OBX,其余 10 只大鼠(n=5,5)不做任何处理。观察两组大鼠的精神运动行为、妊娠率以及性行为、摄食行为、母性行为、社交行为和理毛行为,连续 3 个月每天观察。采用体视学方法检查其 OB、嗅皮质和缰核复合体。研究组的所有动物,尤其是烧灼组的动物,都表现出厌食、营养障碍、体重减轻、精神运动迟缓、性厌恶、理毛行为减少以及社交互动减少,类似于抑郁症状。与对照组相比,研究组的妊娠率、每只母鼠的后代数量和出生体重降低,而死胎数量增加。大体解剖检查发现,研究组所有动物的 OB 均萎缩。组织病理学检查发现,研究组缰核结构有明显的神经元凋亡性丢失。我们发现,OBX 大鼠缰核健康神经元密度的减少与抑郁症状之间存在相关性。我们认为,嗅觉障碍可能通过影响缰核神经元变性导致神经精神障碍。

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