Abstract：
BACKGROUND: Olfactory impairment has been reported in patients with depression and in rodent models of depression. Olfactory epithelium (OE) is the only peripheral neural tissue connected to the brain that has the potential for self-renewal. We hypothesized the olfactory deficit during depression may be related to the dysfunction of OE progenitor cells. The aim of the present study was therefore to evaluate the expansion and neuronal differentiation potency of cultured OE progenitor cells obtained from a rat model of depression.
METHODS: Rats were exposed to chronic unpredictable mild stress procedures to establish a depressive-like state. Depressive-like behavior and olfactory sensing function were then evaluated and compared with control rats. Primary OE progenitor cells were cultured in vitro. The proliferation potency and survival of OE progenitor cells were assessed by 5-Ethynyl-2\'-deoxyuridine staining and Cell Counting Kit-8 (CCK8), respectively, while cellular apoptosis was measured by flow cytometry. The neuronal differentiation potency of OE progenitor cells was evaluated by measurement of the protein and mRNA level of β-3 tubulin, a marker of neural cells. mRNA expression associated with neural stemness was examined by quantitative reverse transcription polymerase chain reaction (RT-PCR).
RESULTS: Depressive-like rats showed decreased olfactory function. OE progenitor cells from depressive-like rats showed reduced cell proliferation/survival and neuronal differentiation potency. Moreover, OE progenitor cells from depressive-like rats showed decreased expression of mRNA related to neural stemness.
CONCLUSIONS: These results indicate the impaired function of OE progenitor cells may contribute to the olfactory deficit observed during depression. The OE may therefore provide a window for the study of depression.
METHODS: Rats were exposed to chronic unpredictable mild stress procedures to establish a depressive-like state. Depressive-like behavior and olfactory sensing function were then evaluated and compared with control rats. Primary OE progenitor cells were cultured in vitro. The proliferation potency and survival of OE progenitor cells were assessed by 5-Ethynyl-2\'-deoxyuridine staining and Cell Counting Kit-8 (CCK8), respectively, while cellular apoptosis was measured by flow cytometry. The neuronal differentiation potency of OE progenitor cells was evaluated by measurement of the protein and mRNA level of β-3 tubulin, a marker of neural cells. mRNA expression associated with neural stemness was examined by quantitative reverse transcription polymerase chain reaction (RT-PCR).
RESULTS: Depressive-like rats showed decreased olfactory function. OE progenitor cells from depressive-like rats showed reduced cell proliferation/survival and neuronal differentiation potency. Moreover, OE progenitor cells from depressive-like rats showed decreased expression of mRNA related to neural stemness.
CONCLUSIONS: These results indicate the impaired function of OE progenitor cells may contribute to the olfactory deficit observed during depression. The OE may therefore provide a window for the study of depression.
摘要：
背景：已经报道了抑郁症患者和啮齿动物抑郁症模型中的嗅觉损害。嗅觉上皮（OE）是唯一与大脑相连的具有自我更新潜力的周围神经组织。我们假设抑郁症期间的嗅觉缺陷可能与OE祖细胞的功能障碍有关。因此，本研究的目的是评估从抑郁症大鼠模型获得的培养的OE祖细胞的扩增和神经元分化能力。
方法：将大鼠暴露于慢性不可预测的轻度应激程序以建立抑郁样状态。然后评估抑郁样行为和嗅觉感知功能，并与对照大鼠进行比较。体外培养原代OE祖细胞。通过5-乙炔基-2'-脱氧尿苷染色和细胞计数试剂盒-8（CCK8）评估OE祖细胞的增殖能力和存活，分别,而细胞凋亡通过流式细胞术测量。通过测量β-3微管蛋白的蛋白质和mRNA水平来评估OE祖细胞的神经元分化能力，神经细胞的标志.通过定量逆转录聚合酶链反应（RT-PCR）检查与神经干性相关的mRNA表达。
结果：抑郁样大鼠嗅觉功能下降。来自抑郁样大鼠的OE祖细胞显示降低的细胞增殖/存活和神经元分化潜能。此外，抑郁样大鼠的OE祖细胞显示与神经干性相关的mRNA表达降低。
结论：这些结果表明，OE祖细胞的功能受损可能是抑郁症期间观察到的嗅觉缺陷的原因。因此，OE可能为抑郁症的研究提供了一个窗口。
方法：将大鼠暴露于慢性不可预测的轻度应激程序以建立抑郁样状态。然后评估抑郁样行为和嗅觉感知功能，并与对照大鼠进行比较。体外培养原代OE祖细胞。通过5-乙炔基-2'-脱氧尿苷染色和细胞计数试剂盒-8（CCK8）评估OE祖细胞的增殖能力和存活，分别,而细胞凋亡通过流式细胞术测量。通过测量β-3微管蛋白的蛋白质和mRNA水平来评估OE祖细胞的神经元分化能力，神经细胞的标志.通过定量逆转录聚合酶链反应（RT-PCR）检查与神经干性相关的mRNA表达。
结果：抑郁样大鼠嗅觉功能下降。来自抑郁样大鼠的OE祖细胞显示降低的细胞增殖/存活和神经元分化潜能。此外，抑郁样大鼠的OE祖细胞显示与神经干性相关的mRNA表达降低。
结论：这些结果表明，OE祖细胞的功能受损可能是抑郁症期间观察到的嗅觉缺陷的原因。因此，OE可能为抑郁症的研究提供了一个窗口。
