Department of Pharmacology, Rungta College of Pharmaceutical Sciences and Research, Kohka-Kurud Road, Bhilai, (C.G.), 490024, India.
Department of Biomedical Engineering, Integrative Biosciences Center, Wayne State University, 6135 Woodward Ave, Detroit, MI, 48202, USA.
Mol Neurobiol. 2021 Mar;58(3):1248-1259. doi: 10.1007/s12035-020-02185-w. Epub 2020 Oct 29.
Olfactory perception and learning play a vital role in the animal's entire life for habituation and survival. Insulin and insulin receptor signaling is well known to modulate the olfactory function and is also involved in the regulation of neurogenesis. A very high density of insulin receptors is present in the olfactory bulb (OB), the brain area involved in the olfactory function, where active adult neurogenesis also takes place. Hence, our study was aimed to explore the effect of intranasal insulin treatment and the involvement of the subventricular zone-olfactory bulb (SVZ-OB) neurogenesis on olfactory discriminative learning and memory in intracerebroventricular streptozotocin (ICV STZ) rat model. Our findings revealed that intranasal insulin treatment significantly increased ICV STZ-induced decrease in the olfactory discriminative learning. No significant change was observed in the post-treatment olfactory memory upon ICV STZ and intranasal insulin treatment. ICV STZ also caused a substantial decline in the SVZ-OB neurogenesis, as indicated by the reduction in the number of 5-bromo-2'-deoxyuridine (BrdU) cells, BrdU Nestin cells, and Doublecortin (DCX) cells, which was reversed by intranasal insulin treatment. Intranasal insulin treatment also increased the number of immature neurons reaching the olfactory bulb (OB) as indicated by an increase in the DCX expression in the OB as compared to the ICV STZ administered group. ICV STZ administration also resulted in the modulation of the expression of the genes regulating postnatal SVZ-OB neurogenesis like Mammalian achaete scute homolog 1 (Mash 1), Neurogenin 2 (Ngn 2), Neuronal differentiation 1 (Neuro D1), and T box brain protein 2 (Tbr 2). Intranasal insulin treatment reverted these changes in gene expression, which might be responsible for the observed increase in the SVZ-OB neurogenesis and hence the olfactory discriminative learning.
嗅觉感知和学习在动物的整个生命周期中对于习惯形成和生存至关重要。胰岛素和胰岛素受体信号通路已被证实可调节嗅觉功能，并且参与神经发生的调节。胰岛素受体在嗅球（OB）中高度表达，OB 是参与嗅觉功能的大脑区域，同时也存在活跃的成年神经发生。因此，我们的研究旨在探讨鼻内胰岛素治疗的效果以及室下区-嗅球（SVZ-OB）神经发生在脑室内链脲佐菌素（ICV STZ）大鼠模型中的嗅觉辨别学习和记忆中的作用。我们的研究结果表明，鼻内胰岛素治疗可显著增加 ICV STZ 诱导的嗅觉辨别学习能力下降。在接受 ICV STZ 和鼻内胰岛素治疗后，嗅觉记忆没有明显变化。ICV STZ 还导致 SVZ-OB 神经发生显著减少，表现为 5-溴-2'-脱氧尿苷（BrdU）细胞、BrdU 巢蛋白细胞和双皮质素（DCX）细胞数量减少，而鼻内胰岛素治疗可逆转这一现象。鼻内胰岛素治疗还增加了到达嗅球（OB）的未成熟神经元数量，这表现为与接受 ICV STZ 治疗的组相比，OB 中 DCX 表达增加。ICV STZ 给药还导致调节 SVZ-OB 神经发生的基因表达发生改变，如哺乳动物achaete scute 同源物 1（Mash 1）、神经生成素 2（Ngn 2）、神经元分化 1（Neuro D1）和 T 盒脑蛋白 2（Tbr 2）。鼻内胰岛素治疗可逆转这些基因表达的变化，这可能是观察到的 SVZ-OB 神经发生增加和嗅觉辨别学习能力增强的原因。
