Vadodaria Krishna C, Yanpallewar Sudhirkumar U, Vadhvani Mayur, Toshniwal Devyani, Liles L Cameron, Rommelfanger Karen S, Weinshenker David, Vaidya Vidita A
Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India, India.
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA, USA.
Neurosci Lett. 2017 Mar 22;644:76-82. doi: 10.1016/j.neulet.2017.02.060. Epub 2017 Feb 23.
The adult rodent piriform cortex has been reported to harbor immature neurons that express markers associated with neurodevelopment and plasticity, namely polysialylated neural cell adhesion molecule (PSA-NCAM) and doublecortin (DCX). We characterized the expression of PSA-NCAM and DCX across the rostrocaudal axis of the rat piriform cortex and observed higher numbers of PSA-NCAM and DCX positive cells in the posterior subdivision. As observed in the rat piriform cortex, Nestin-GFP reporter mice also revealed a similar gradient of GFP-positive cells with an increasing rostro-caudal gradient of expression. Given the extensive noradrenergic innervation of the piriform cortex and its role in regulating piriform cortex function and synaptic plasticity, we addressed the influence of norepinephrine (NE) on piriform cortex plasticity marker expression. Depletion of NE by treatment with the noradrenergic neurotoxin DSP-4 significantly increased the number of DCX and PSA-NCAM immunopositive cells in the piriform cortex of adult rats. Similarly, DSP-4 treated Nestin-GFP reporter mice revealed a robust induction of GFP-positive cells within the piriform cortex following NE depletion. Genetic loss of NE in dopamine β-hydroxylase knockout (Dbh -/-) mice phenocopied the effects of DSP-4, with an increase noted in PSA-NCAM and DCX positive cells in the piriform cortex. Further, chronic α-adrenergic receptor stimulation with the agonist guanabenz increased PSA-NCAM and DCX positive cells in the piriform cortex of adult rats and GFP-positive cells in the piriform cortex of Nestin-GFP mice. By contrast, chronic α-adrenergic receptor blockade with the antagonist yohimbine reduced PSA-NCAM and DCX positive cells in the piriform cortex of adult rats. Our results provide novel evidence for a role of NE in regulating the expression of plasticity markers, including PSA-NCAM, DCX, and nestin, within the adult mouse and rat piriform cortex.
据报道，成年啮齿动物的梨状皮质中存在表达与神经发育和可塑性相关标志物的未成熟神经元，即多唾液酸神经细胞黏附分子（PSA-NCAM）和双皮质素（DCX）。我们对大鼠梨状皮质 rostrocaudal 轴上 PSA-NCAM 和 DCX 的表达进行了表征，发现在后部分区中 PSA-NCAM 和 DCX 阳性细胞数量更多。正如在大鼠梨状皮质中观察到的那样，Nestin-GFP 报告基因小鼠也显示出 GFP 阳性细胞的类似梯度，其表达沿 rostro-caudal 梯度增加。鉴于梨状皮质广泛的去甲肾上腺素能神经支配及其在调节梨状皮质功能和突触可塑性中的作用，我们研究了去甲肾上腺素（NE）对梨状皮质可塑性标志物表达的影响。用去甲肾上腺素能神经毒素 DSP-4 处理耗尽 NE 后，成年大鼠梨状皮质中 DCX 和 PSA-NCAM 免疫阳性细胞的数量显著增加。同样，经 DSP-4 处理的 Nestin-GFP 报告基因小鼠在 NE 耗尽后，梨状皮质内 GFP 阳性细胞出现了强烈诱导。多巴胺β-羟化酶基因敲除（Dbh -/-）小鼠中 NE 的基因缺失模拟了 DSP-4 的作用，梨状皮质中 PSA-NCAM 和 DCX 阳性细胞数量增加。此外，用激动剂胍那苄进行慢性α-肾上腺素能受体刺激可增加成年大鼠梨状皮质中 PSA-NCAM 和 DCX 阳性细胞以及 Nestin-GFP 小鼠梨状皮质中 GFP 阳性细胞的数量。相比之下，用拮抗剂育亨宾进行慢性α-肾上腺素能受体阻断可减少成年大鼠梨状皮质中 PSA-NCAM 和 DCX 阳性细胞的数量。我们的结果为 NE 在调节成年小鼠和大鼠梨状皮质内可塑性标志物（包括 PSA-NCAM、DCX 和巢蛋白）的表达中所起的作用提供了新证据。
