Change in Brain Plasmalogen Composition by Exposure to Prenatal Undernutrition Leads to Behavioral Impairment of Rats
Change in Brain Plasmalogen Composition by Exposure to Prenatal Undernutrition Leads to Behavioral Impairment of Rats
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DOI：
10.1523/jneurosci.2721-18.2019
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发表时间：
2019-08
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通讯作者：
Kodai Hino;Shunya Kaneko;T. Harasawa;Tomoko Kimura;S. Takei;M. Shinohara;Fumiyoshi Yamazaki;Shin-ya Morita;Shumpei Sato;Yoshihito Kubo;Tadaaki Kono;M. Setou;M. Yoshioka;J. Fujino;H. Sugihara;Hideto Kojima;N. Yamada;J. Udagawa
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作者：
Kodai Hino;Shunya Kaneko;T. Harasawa;Tomoko Kimura;S. Takei;M. Shinohara;Fumiyoshi Yamazaki;Shin-ya Morita;Shumpei Sato;Yoshihito Kubo;Tadaaki Kono;M. Setou;M. Yoshioka;J. Fujino;H. Sugihara;Hideto Kojima;N. Yamada;J. Udagawa
流行病学研究表明，怀孕期间营养不良会影响后代易患发育和精神障碍。动物研究表明，母亲营养不良会导致行为障碍，这与单胺能系统的改变和大脑中的炎症有关。在这项研究中，我们专注于乙醇胺血浆酶原的大脑作为一个可能的贡献者的行为障碍观察到的后代暴露于母亲营养不良。妊娠第5.5天（GD）和GD 10.5天之间的母体食物或蛋白质限制导致大鼠雄性成年后代活动过度。与磷脂生物合成相关的基因被发现在PFC中被激活，而不是在NAcc或纹状体中，在产前营养不良的后代中。与这些基因激活相对应，使用质谱成像在PFC中观察到乙醇胺缩醛磷脂（18：0 p-22：6）增加。在暴露于产前营养不良的后代中观察到大量的交叉和在中心区域停留的长时间，并通过静脉注射掺入脂质体的乙醇胺缩醛磷脂（18：0 p-22：6）在成年大鼠中进行模拟。此外，血浆酶原（18：0 p-22：6）仅在PFC中增加，而不在NAcc或纹状体中增加。这些结果表明，脑缩醛磷脂是控制行为的关键分子之一，其脂质体注射是一种潜在的治疗认知障碍的方法。母亲营养不良与发育和精神障碍相关。在这里，我们发现，母亲在怀孕早期营养不良导致大鼠雄性后代的活动过度，并诱导磷脂合成酶的基因激活和PFC中乙醇胺缩醛磷脂（18：0 p-22：6）水平的升高。静脉注射乙醇胺缩醛磷脂（18：0 p-22：6）纳入脂质体保持交叉活性，并且该活性被限制在中心区域很长一段时间，在产前营养不良的后代与异常行为。此外，注射后大鼠PFC中乙醇胺缩醛磷脂（18：0 p-22：6）的量增加。我们的研究结果表明，脑缩醛磷脂是控制行为的关键分子之一，其脂质体注射是一种潜在的治疗认知障碍的方法。
Epidemiological studies suggest that poor nutrition during pregnancy influences offspring predisposition to experience developmental and psychiatric disorders. Animal studies have shown that maternal undernutrition leads to behavioral impairment, which is linked to alterations in monoaminergic systems and inflammation in the brain. In this study, we focused on the ethanolamine plasmalogen of the brain as a possible contributor to behavioral disturbances observed in offspring exposed to maternal undernutrition. Maternal food or protein restriction between gestational day (GD) 5.5 and GD 10.5 resulted in hyperactivity of rat male adult offspring. Genes related to the phospholipid biosynthesis were found to be activated in the PFC, but not in the NAcc or striatum, in the offspring exposed to prenatal undernutrition. Corresponding to these gene activations, increased ethanolamine plasmalogen (18:0p-22:6) was observed in the PFC using mass spectrometry imaging. A high number of crossings and the long time spent in the center area were observed in the offspring exposed to prenatal undernutrition and were mimicked in adult rats via the intravenous injection of ethanolamine plasmalogen (18:0p-22:6) incorporated into the liposome. Additionally, plasmalogen (18:0p-22:6) increased only in the PFC, and not in the NAcc or striatum. These results suggest that brain plasmalogen is one of the key molecules to control behavior, and its injection using liposome is a potential therapeutic approach for cognitive impairment. SIGNIFICANCE STATEMENT Maternal undernutrition correlates to developmental and psychiatric disorders. Here, we found that maternal undernutrition in early pregnancy led to hyperactivity in rat male offspring and induced gene activation of phospholipid-synthesizing enzyme and elevation of ethanolamine plasmalogen (18:0p-22:6) level in the PFC. Intravenous injection of ethanolamine plasmalogen (18:0p-22:6) incorporated into the liposome maintained crossing activity and the activity was circumscribed to the center area for a long time period, as in prenatally undernourished offspring with aberrant behavior. Furthermore, the amount of ethanolamine plasmalogen (18:0p-22:6) increased in the PFC of the rat after injection. Our result suggests that brain plasmalogen is one of the key molecules to control behavior and that its injection using liposome is a potential therapeutic approach for cognitive impairment.