PDF(Pubmed)
Abstract：
This study used a marsupial Monodelphis domestica, which is born very immature and most of its development is postnatal without placental protection. RNA-sequencing (RNA-Seq) was used to identify the expression of influx and efflux transporters (ATP-binding cassettes [ABCs] and solute carriers [SLCs]) and metabolizing enzymes in brains of newborn to juvenile Monodelphis. Results were compared to published data in the developing eutherian rat. To test the functionality of these transporters at similar ages, the entry of paracetamol (acetaminophen) into the brain and cerebrospinal fluid (CSF) was measured using liquid scintillation counting following a single administration of the drug along with its radiolabelled tracer [3H]. Drug permeability studies found that in Monodelphis, brain entry of paracetamol was already restricted at P5; it decreased further in the first week of life and then remained stable until the oldest age group tested (P110). Transcriptomic analysis of Monodelphis brain showed that expression of transporters and their metabolizing enzymes in early postnatal (P) pups (P0, P5, and P8) was relatively similar, but by P109, many more transcripts were identified. When transcriptomes of newborn Monodelphis brain and E19 rat brain and placenta were compared, several transporters present in the rat placenta were also found in the newborn Monodelphis brain. These were absent from E19 rat brain but were present in the adult rat brain. These data indicate that despite its extreme immaturity, the newborn Monodelphis brain may compensate for the lack of placental protection during early brain development by upregulating protective mechanisms, which in eutherian animals are instead present in the placenta.
摘要：
这项研究使用了一种有袋动物，出生时非常不成熟，其大部分发育是产后没有胎盘保护。RNA测序（RNA-Seq）用于鉴定新生至幼年Monodelphis的大脑中流入和流出转运蛋白（ATP结合盒[ABC]和溶质载体[SLC]）和代谢酶的表达。将结果与发育中的Eutherian大鼠的公开数据进行比较。为了测试这些运输者在相似年龄的功能，对乙酰氨基酚(对乙酰氨基酚)进入脑和脑脊液(CSF)的情况是在单次给药后使用液体闪烁计数及其放射性标记示踪剂[3H]测量的.药物渗透性研究发现，在Monodelphis中，对乙酰氨基酚的大脑进入在P5时已经受到限制;它在生命的第一周进一步下降,然后保持稳定,直到测试的最老年龄组(P110).Monodelphis脑的转录组学分析表明，出生后早期（P）幼崽（P0，P5和P8）中转运体及其代谢酶的表达相对相似，但是通过P109，发现了更多的转录本。当比较新生Monodelphis脑和E19大鼠脑和胎盘的转录组时，在新生的Monodelphis脑中也发现了几种存在于大鼠胎盘中的转运蛋白。这些在E19大鼠脑中不存在，但在成年大鼠脑中存在。这些数据表明，尽管它极度不成熟，新生儿Monodelphis大脑可以通过上调保护机制来补偿早期大脑发育过程中胎盘保护的缺乏，而在伊万西亚动物中却存在于胎盘中。
