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发育性血清素信号失调影响前额叶儿茶酚胺能神经支配和皮质完整性。

Perturbed Developmental Serotonin Signaling Affects Prefrontal Catecholaminergic Innervation and Cortical Integrity.

机构信息

Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, Department of Molecular Animal Physiology, Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Nijmegen, Geert Grooteplein Zuid 28, 6525 GA, Nijmegen, The Netherlands.

Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, Department of Cognitive Neuroscience, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

出版信息

Mol Neurobiol. 2019 Feb;56(2):1405-1420. doi: 10.1007/s12035-018-1105-x. Epub 2018 Jun 9.

DOI:10.1007/s12035-018-1105-x
PMID:29948943
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6400880/
Abstract

Proper development of the medial prefrontal cortex (mPFC), crucial for correct cognitive functioning, requires projections from, among others, the serotonergic (5-HT) and catecholaminergic systems, but it is unclear how these systems influence each other during development. Here, we describe the parallel development of the 5-HT and catecholaminergic prefrontal projection systems in rat and demonstrate a close engagement of both systems in the proximity of Cajal-Retzius cells. We further show that in the absence of the 5-HT transporter (5-HTT), not only the developing 5-HT but also the catecholaminergic system, including their projections towards the mPFC, are affected. In addition, the layer identity of the mPFC neurons and reelin-positive interneuron number and integration are altered in the absence of the 5-HTT. Together, our data demonstrate a functional interplay between the developing mPFC 5-HT and catecholaminergic systems, and call for a holistic approach in studying neurotransmitter systems-specific developmental consequences for adult behavior, to eventually allow the design of better treatment strategies for neuropsychiatric disorders.

摘要

内侧前额叶皮层（mPFC）的正常发育对于正确的认知功能至关重要，需要来自 5-羟色胺（5-HT）和儿茶酚胺能系统等的投射，但目前尚不清楚这些系统在发育过程中如何相互影响。在这里，我们描述了大鼠中 5-HT 和儿茶酚胺能前额叶投射系统的平行发育，并证明了这两个系统在 Cajal-Retzius 细胞附近的紧密参与。我们进一步表明，在缺乏 5-HT 转运体（5-HTT）的情况下，不仅发育中的 5-HT，而且包括其向 mPFC 的投射在内的儿茶酚胺能系统也受到影响。此外，在缺乏 5-HTT 的情况下，mPFC 神经元的层身份以及 reelin 阳性中间神经元的数量和整合也发生改变。总之，我们的数据表明发育中的 mPFC 5-HT 和儿茶酚胺能系统之间存在功能相互作用，并呼吁在研究特定神经递质系统对成年行为的发育后果时采取整体方法，最终为神经精神疾病设计更好的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a26/6400880/25a06b1c20ea/12035_2018_1105_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a26/6400880/74329c02966e/12035_2018_1105_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a26/6400880/29260d85c504/12035_2018_1105_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a26/6400880/d9d70d026553/12035_2018_1105_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a26/6400880/6a27634b7fee/12035_2018_1105_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a26/6400880/689a95e56202/12035_2018_1105_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a26/6400880/5c98a932b34e/12035_2018_1105_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a26/6400880/25a06b1c20ea/12035_2018_1105_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a26/6400880/74329c02966e/12035_2018_1105_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a26/6400880/b934ba816f64/12035_2018_1105_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a26/6400880/29260d85c504/12035_2018_1105_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a26/6400880/d9d70d026553/12035_2018_1105_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a26/6400880/6a27634b7fee/12035_2018_1105_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a26/6400880/689a95e56202/12035_2018_1105_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a26/6400880/5c98a932b34e/12035_2018_1105_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a26/6400880/25a06b1c20ea/12035_2018_1105_Fig8_HTML.jpg

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