Adult neurogenesis, analogous to early development, is comprised of several, often concomitant, processes including proliferation, differentiation, and formation of synaptic connections. However, due to continual, asynchronous turn-over, newly-born adult olfactory sensory neurons (OSNs) must integrate into existing circuitry. Additionally, OSNs express high levels of cellular prion protein (PrPC), particularly in the axon, which implies a role in this cell type. The cellular prion has been shown to be important for proper adult OSN neurogenesis primarily by stabilizing mature olfactory neurons within this circuitry. However, the role of PrPC on each specific adult neurogenic processes remains to be investigated in detail. To tease out the subtle effects of prion protein expression level, a large population of regenerating neurons must be investigated. The thyroid drug methimazole (MTZ) causes nearly complete OSN loss in rodents and is used as a model of acute olfactory injury, providing a mechanism to induce synchronized OSN regeneration. This study investigated the effect of PrPC on adult neurogenesis after acute nasotoxic injury. Altered PrPC levels affected olfactory sensory epithelial (OSE) regeneration, cell proliferation, and differentiation. Attempts to investigate the role of PrPC level on axon regeneration did not support previous studies, and glomerular targeting did not recover to vehicle-treated levels, even by 20 weeks. Together, these studies demonstrate that the cellular prion protein is critical for regeneration of neurons, whereby increased PrPC levels promote early neurogenesis, and that lack of PrPC delays the regeneration of this tissue after acute injury.

中文翻译：

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细胞朊病毒蛋白促进急性鼻毒性损伤后的神经元再生。


成人神经发生，类似于早期发育，由几个通常伴随的过程组成，包括增殖、分化和突触连接的形成。然而，由于持续的异步转换，新生的成年嗅觉感觉神经元（OSN）必须集成到现有的电路中。此外，OSN 表达高水平的细胞朊病毒蛋白 (PrPC)，特别是在轴突中，这意味着在这种细胞类型中发挥作用。细胞朊病毒已被证明对正常的成人 OSN 神经发生很重要，主要是通过稳定该电路内的成熟嗅觉神经元。然而，PrPC 对每个特定成人神经发生过程的作用仍有待详细研究。为了弄清楚朊病毒蛋白表达水平的微妙影响，必须研究大量的再生神经元。甲状腺药物甲硫咪唑 (MTZ) 会导致啮齿动物几乎完全丧失 OSN，并被用作急性嗅觉损伤的模型，提供了诱导同步 OSN 再生的机制。本研究调查了 PrPC 对急性鼻毒性损伤后成人神经发生的影响。 PrPC 水平的改变影响嗅觉上皮 (OSE) 再生、细胞增殖和分化。尝试调查 PrPC 水平对轴突再生的作用并不支持之前的研究，并且肾小球靶向即使到了 20 周也没有恢复到载体治疗的水平。总之，这些研究表明细胞朊病毒蛋白对于神经元的再生至关重要，因此 PrPC 水平的增加可促进早期神经发生，而 PrPC 的缺乏会延迟急性损伤后该组织的再生。