Systemic innate immune response induces death of olfactory receptor neurons in Drosophila
Systemic innate immune response induces death of olfactory receptor neurons in Drosophila
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系统先天免疫反应诱导果蝇嗅觉受体神经元死亡
DOI：
10.1111/gtc.12914
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发表时间：
2022
期刊：
影响因子：
2.1
通讯作者：
Takahiro Chihara
中科院分区：
文献类型：
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作者：
Kenichi Takeuchi;Daichi Honda;Misako Okumura;Masayuki Miura;Takahiro Chihara
众所周知，在正常衰老和神经退行性疾病期间，神经功能会下降。然而，由于大脑的正常老化而导致的功能损害的机制却知之甚少。先前，我们报道了在正常衰老过程中，负责诱导细胞凋亡的caspase-3蛋白水解酶在嗅觉感受器神经元中被激活，尤其是在果蝇或42b神经元中。在此，我们研究了与年龄相关的caspase-3样蛋白水解酶激活和Or42b神经元细胞死亡的分子机制。幼龄和老年蝇触角的基因表达谱显示，抗菌肽的表达显著上调，提示存在激活的先天免疫反应。与此观察一致的是，抑制或激活先天免疫途径分别导致Or42b神经元中延迟或早熟的细胞死亡。因此，Or42b神经元天然免疫途径的自主激活可能不是其年龄相关死亡所必需的，而全身天然免疫反应诱导Or42b神经元中caspase-3样蛋白酶的激活，这表明这些神经元的死亡是非细胞自主调节的。我们提出了先天免疫反应和嗅觉神经元在正常老化过程中死亡之间的可能联系。
Neural functions are known to decline during normal aging and neurodegenerative diseases. However, the mechanisms of functional impairment owing to the normal aging of the brain are poorly understood. Previously, we reported that caspase‐3‐like protease, the protease responsible for inducing apoptosis, is activated in a subset of olfactory receptor neurons (ORNs), especially inDrosophilaOr42b neurons, during normal aging. Herein, we investigated the molecular mechanism underlying age‐related caspase‐3‐like protease activation and cell death in Or42b neurons. Gene expression profiling of young and aged fly antenna showed that the expression of antimicrobial peptides was significantly upregulated, suggesting an activated innate immune response. Consistent with this observation, inhibition or activation of the innate immune pathway caused delayed or precocious cell death, respectively, in Or42b neurons. Accordingly, autonomous cell activation of the innate immune pathway in Or42b neurons is not likely required for their age‐related death, whereas the systemic innate immune response induces caspase‐3‐like protease activation in Or42b neurons; this indicated that the death of these neurons is regulated non‐cell autonomously. We propose a possible link between the innate immune response and the death of olfactory neurons during normal aging.