Coviello Simona, Gramuntell Yaiza, Castillo-Gomez Esther, Nacher Juan
Neurobiology Unit, Program in Neurosciences and Institute of Biotechnology and Biomedicine (BIOTECMED), Universitat de València, Burjassot, Spain.
Department of Medicine, School of Medical Sciences, Universitat Jaume I, Castellón de la Plana, Spain.
Front Neurosci. 2020 Oct 6;14:574234. doi: 10.3389/fnins.2020.574234. eCollection 2020.
The layer II of the adult piriform cortex (PCX) contains a numerous population of immature neurons. Interestingly, in both mice and rats, most, if not all, these cells have an embryonic origin. Moreover, recent studies from our laboratory have shown that they progressively mature into typical excitatory neurons of the PCX layer II. Therefore, the adult PCX is considered a "non-canonical" neurogenic niche. These immature neurons express the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a molecule critical for different neurodevelopmental processes. Dopamine (DA) is a relevant neurotransmitter in the adult CNS, which also plays important roles in neural development and adult plasticity, including the regulation of PSA-NCAM expression. In order to evaluate the hypothetical effects of pharmacological modulation of dopaminergic neurotransmission on the differentiation of immature neurons of the adult PCX, we studied dopamine D2 receptor (D2r) expression in this region and the relationship between dopaminergic fibers and immature neurons (defined by PSA-NCAM expression). In addition, we analyzed the density of immature neurons after chronic treatments with an antagonist and an agonist of D2r: haloperidol and PPHT, respectively. Many dopaminergic fibers were observed in close apposition to PSA-NCAM-expressing neurons, which also coexpressed D2r. Chronic treatment with haloperidol significantly increased the number of PSA-NCAM immunoreactive cells, while PPHT treatment decreased it. These results indicate a prominent role of dopamine, through D2r and PSA-NCAM, on the regulation of the final steps of development of immature neurons in the adult PCX.
成年梨状皮层（PCX）的第二层包含大量未成熟神经元。有趣的是，在小鼠和大鼠中，这些细胞中的大多数（如果不是全部的话）都起源于胚胎。此外，我们实验室最近的研究表明，它们会逐渐成熟为PCX第二层的典型兴奋性神经元。因此，成年PCX被认为是一个“非典型”的神经发生微环境。这些未成熟神经元表达神经细胞黏附分子的多唾液酸化形式（PSA-NCAM），这是一种对不同神经发育过程至关重要的分子。多巴胺（DA）是成年中枢神经系统中的一种相关神经递质，它在神经发育和成年可塑性中也发挥着重要作用，包括对PSA-NCAM表达的调节。为了评估多巴胺能神经传递的药理学调节对成年PCX未成熟神经元分化的假设影响，我们研究了该区域中多巴胺D2受体（D2r）的表达以及多巴胺能纤维与未成熟神经元（由PSA-NCAM表达定义）之间的关系。此外，我们分别用D2r的拮抗剂和激动剂：氟哌啶醇和PPHT进行慢性处理后，分析了未成熟神经元的密度。观察到许多多巴胺能纤维与表达PSA-NCAM的神经元紧密相邻，这些神经元也共表达D2r。氟哌啶醇慢性处理显著增加了PSA-NCAM免疫反应性细胞的数量，而PPHT处理则使其减少。这些结果表明，多巴胺通过D2r和PSA-NCAM在调节成年PCX未成熟神经元发育的最后步骤中发挥着重要作用。
