Abellán-Álvaro María, Teruel-Sanchis Anna, Madeira Maria Francisca, Lanuza Enrique, Santos Mónica, Agustín-Pavón Carmen
Unitat Mixta d'Investigació en Neuroanatomia Funcional, Departament de Biologia Cel⋅lular, Biologia Funcional i Antropologia Física, Universitat de València, València, Spain.
CNC-UC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
Front Neurosci. 2024 Sep 16;18:1446912. doi: 10.3389/fnins.2024.1446912. eCollection 2024.
The olfactory system is a niche of continuous structural plasticity, holding postnatal proliferative neurogenesis in the olfactory bulbs and a population of immature neurons in the piriform cortex. These neurons in the piriform cortex are generated during embryonic development, retain the expression of immaturity markers such as doublecortin, and slowly mature and integrate into the olfactory circuit as the animal ages. To study how early life experiences affect this population of cortical immature neurons, we submitted mice of the C57/Bl6J strain to a protocol of maternal separation for 3 h per day from postnatal day 3 to postnatal day 21. Control mice were continuously with their mothers. After weaning, mice were undisturbed until 6 weeks of age, when they were weighted and tested in the elevated plus-maze, a standard test for anxiety-like behavior, to check for phenotypical effects. Mice were then perfused, and their brains processed for the immunofluorescent detection of doublecortin and the endogenous proliferation marker Ki67. We found that maternal separation induced a significant increase in the body weight of males, but not females. Further, maternally separated mice displayed increased exploratory-like behavior (i.e., head dipping, velocity and total distance traveled in the elevated plus maze), but no significant differences in anxiety-like behavior or corticosterone levels after behavioral testing. Finally, we observed a significant increase in the number of complex doublecortin neurons in the piriform cortex, but not in the olfactory bulbs, of mice submitted to maternal separation. Interestingly, most doublecortin neurons in the piriform cortex, but not the olfactory bulb, express the epigenetic reader MeCP2. In summary, mild early life stress results, during adolescence, in a male-specific increase in body weight, alteration of the exploratory behaviors, and an increase in doublecortin neurons in the piriform cortex, suggesting an alteration in their maturation process.
嗅觉系统是一个具有持续结构可塑性的微环境，在嗅球中存在出生后增殖性神经发生，在梨状皮质中存在一群未成熟神经元。梨状皮质中的这些神经元在胚胎发育期间产生，保留诸如双皮质素等未成熟标记物的表达，并随着动物年龄增长而缓慢成熟并整合到嗅觉回路中。为了研究早期生活经历如何影响这群皮质未成熟神经元，我们将C57/Bl6J品系的小鼠从出生后第3天到出生后第21天每天进行3小时的母婴分离实验。对照小鼠则一直与母亲在一起。断奶后，小鼠在6周龄前不受干扰，之后对它们进行称重，并在高架十字迷宫（一种用于检测焦虑样行为的标准测试）中进行测试，以检查是否有表型效应。然后对小鼠进行灌注，并对其大脑进行处理，用于双皮质素和内源性增殖标记物Ki67的免疫荧光检测。我们发现母婴分离导致雄性小鼠体重显著增加，而雌性小鼠体重未增加。此外，母婴分离的小鼠表现出探索样行为增加（即头部下垂、速度和在高架十字迷宫中行进的总距离），但在行为测试后焦虑样行为或皮质酮水平没有显著差异。最后，我们观察到接受母婴分离的小鼠梨状皮质中复杂双皮质素神经元数量显著增加，但嗅球中未增加。有趣的是，梨状皮质中的大多数双皮质素神经元（而非嗅球中的）表达表观遗传阅读器MeCP2。总之，轻度的早期生活应激在青春期导致雄性小鼠体重特异性增加、探索行为改变以及梨状皮质中双皮质素神经元增加，这表明它们的成熟过程发生了改变。
