Zoratto Francesca, Altabella Luisa, Tistarelli Naomi, Laviola Giovanni, Adriani Walter, Canese Rossella
Center Behavioral Sciences and Mental Health, Istituto Superiore di Sanità, Rome, Italy.
Core Facilities, Istituto Superiore di Sanità, Rome, Italy.
Front Behav Neurosci. 2018 Sep 24;12:208. doi: 10.3389/fnbeh.2018.00208. eCollection 2018.
Adolescence is an age of transition when most brain structures undergo drastic modifications, becoming progressively more interconnected and undergoing several changes from a metabolic and structural viewpoint. In the present study, three MR techniques are used in rats to investigate how metabolites, structures and patterns of connectivity do change. We focused in particular on areas belonging to the limbic system, across three post-weaning developmental stages: from "early" (PND 21-25) to "mid" (i.e., a juvenile transition, PND 28-32) and then to "late" (i.e., the adolescent transition, PND 35-39). The rs-fMRI data, with comparison between early and mid (juvenile transition) age-stage rats, highlights patterns of enhanced connectivity from both Striata to both Hippocampi and from there to (left-sided) Nucleus accumbens (NAcc) and Orbitofrontal Cortex (OFC). Also, during this week there is a maturation of pathways from right Striatum to ipsilateral NAcc, from right OFC to ipsilateral NAcc and vice versa, from left Prefrontal Cortex to ipsilateral OFC and eventually from left Striatum, NAcc and Prefrontal Cortex to contralateral OFC. After only 1 week, in late age-stage rats entering into adolescence, the first pathway mentioned above keeps on growing while other patterns appear: both NAcc are reached from contralateral Striatum, right Hippocampus from both Amygdalae, and left NAcc -further- from right Hippocampus. It's interesting to notice the fact that, independently from the age when these connections develop, Striata of both hemispheres send axons to both Hippocampi and both NAcc sides, both Hippocampi reach left NAcc and OFC and finally both NAcc sides reach right OFC. Intriguingly, the Striatum only indirectly reaches the OFC by passing through Hippocampus and NAcc. Data obtained with DTI highlight how adolescents' neurite density may be affected within sub-cortical gray matter, especially for NAcc and OFC at "late" age-stage (adolescence). Finally, levels of metabolites were investigated by 1H-MRS in the anterior part of the hippocampus: we put into evidence an increase in myo-inositol during juvenile transition and a taurine reduction plus a total choline increase during adolescent transition. In this paper, the aforementioned pattern guides the formulation of hypotheses concerning the correlation between the establishment of novel brain connections and the emergence of behavioral traits that are typical of adolescence.
青春期是一个过渡时期，在此期间大多数脑结构会经历剧烈变化，从代谢和结构角度来看，它们之间的联系会越来越紧密，并发生多种变化。在本研究中，我们对大鼠使用了三种磁共振技术，以研究代谢物、结构和连接模式是如何变化的。我们特别关注了处于断奶后三个发育阶段的边缘系统区域：从“早期”（出生后第21 - 25天）到“中期”（即幼年过渡期，出生后第28 - 32天），再到“晚期”（即青春期过渡期，出生后第35 - 39天）。静息态功能磁共振成像（rs - fMRI）数据显示，在比较早期和中期（幼年过渡期）的大鼠时，从双侧纹状体到双侧海马体，再从海马体到（左侧）伏隔核（NAcc）和眶额皮质（OFC）的连接增强模式十分明显。此外，在这一周内，从右侧纹状体到同侧NAcc、从右侧OFC到同侧NAcc以及反之从左侧前额叶皮质到同侧OFC，最终从左侧纹状体、NAcc和前额叶皮质到对侧OFC的神经通路逐渐成熟。仅仅1周后，进入青春期的晚期大鼠出现了上述提到的第一条通路持续发展，同时还出现了其他模式：从对侧纹状体到达双侧NAcc，从双侧杏仁核到达右侧海马体，并从右侧海马体进一步到达左侧NAcc。有趣的是，无论这些连接在什么年龄形成，双侧半球的纹状体都会向双侧海马体和双侧NAcc发送轴突，双侧海马体都会到达左侧NAcc和OFC，最终双侧NAcc都会到达右侧OFC。引人注目的是，纹状体仅通过海马体和NAcc间接到达OFC。弥散张量成像（DTI）获得的数据突出显示了青少年的神经突密度在皮质下灰质中可能受到的影响，特别是在“晚期”（青春期）的NAcc和OFC区域。最后，我们通过氢质子磁共振波谱（1H - MRS）研究了海马体前部的代谢物水平：我们发现，在幼年过渡期肌醇增加，在青春期过渡期牛磺酸减少且总胆碱增加。在本文中，上述模式为有关新脑连接的建立与青春期典型行为特征出现之间相关性的假设形成提供了指导。
