Barbara Nikolic, Sara Trnski-Levak, Kristina Kosic, Matea Drlje, Ivan Banovac, Dubravka Hranilovic, Natasa Jovanov-Milosevic
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引用次数: 0
摘要
引言 围产期的不利因素会减少胎儿大脑的氧气供应，导致各种缺氧性脑损伤，从而在不同方面损害大脑发育的规律性。为了研究儿茶酚胺能对早期缺氧损伤与青春期行为异常之间联系的贡献，我们使用了之前建立的围产期缺氧大鼠模型，但将低压条件改为常压条件。对一部分动物的固有垂直运动、感觉运动功能和空间学习能力进行了研究，以明确探索行为改变的背景。最后，研究了31只大鼠中脑和脑桥中多巴胺（DA）和去甲肾上腺素的浓度，以及海马和丘脑中DA受体D1和D2基因及其下游靶标（DA和cAMP调节磷蛋白、蛋白激酶A调节亚基Mr 32 kDa和蛋白磷酸酶1抑制剂-5）的相对表达。结果 与低压条件下相比，本研究中大鼠探索和认知方面行为的改变程度较小，这表明常压条件减轻了缺氧损伤。探索性饲养的增加是最突出的后果，其背景是空间学习能力受损。在受影响的大鼠中，发现中脑/大脑皮质 DA 含量增加，丘脑中 DA 受体及其下游元件的 mRNA 含量也增加，但海马中的情况并非如此。因此，丘脑是除公认的纹状体之外，通过 DA 信号传递参与介导缺氧对行为影响的另一个结构。
Lasting mesothalamic dopamine imbalance and altered exploratory behavior in rats after a mild neonatal hypoxic event
Introduction
Adversities during the perinatal period can decrease oxygen supply to the fetal brain, leading to various hypoxic brain injuries, which can compromise the regularity of brain development in different aspects. To examine the catecholaminergic contribution to the link between an early-life hypoxic insult and adolescent behavioral aberrations, we used a previously established rat model of perinatal hypoxia but altered the hypobaric to normobaric conditions.
Methods
Exploratory and social behavior and learning abilities were tested in 70 rats of both sexes at adolescent age. Inherent vertical locomotion, sensory-motor functions and spatial learning abilities were explored in a subset of animals to clarify the background of altered exploratory behavior. Finally, the concentrations of dopamine (DA) and noradrenaline in midbrain and pons, and the relative expression of genes for DA receptors D1 and D2, and their down-stream targets (DA- and cAMP-regulated phosphoprotein, Mr 32 kDa, the regulatory subunit of protein kinase A, and inhibitor-5 of protein phosphatase 1) in the hippocampus and thalamus were investigated in 31 rats.
Results
A lesser extent of alterations in exploratory and cognitive aspects of behavior in the present study suggests that normobaric conditions mitigate the hypoxic injury compared to the one obtained under hypobaric conditions. Increased exploratory rearing was the most prominent consequence, with impaired spatial learning in the background. In affected rats, increased midbrain/pons DA content, as well as mRNA levels for DA receptors and their down-stream elements in the thalamus, but not the hippocampus, were found.
Conclusion
We can conclude that a mild hypoxic event induced long-lasting disbalances in mesothalamic DA signaling, contributing to the observed behavioral alterations. The thalamus was thereby indicated as another structure, besides the well-established striatum, involved in mediating hypoxic effects on behavior through DA signaling.
期刊介绍：
Frontiers in Integrative Neuroscience publishes rigorously peer-reviewed research that synthesizes multiple facets of brain structure and function, to better understand how multiple diverse functions are integrated to produce complex behaviors. Led by an outstanding Editorial Board of international experts, this multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
Our goal is to publish research related to furthering the understanding of the integrative mechanisms underlying brain functioning across one or more interacting levels of neural organization. In most real life experiences, sensory inputs from several modalities converge and interact in a manner that influences perception and actions generating purposeful and social behaviors. The journal is therefore focused on the primary questions of how multiple sensory, cognitive and emotional processes merge to produce coordinated complex behavior. It is questions such as this that cannot be answered at a single level – an ion channel, a neuron or a synapse – that we wish to focus on. In Frontiers in Integrative Neuroscience we welcome in vitro or in vivo investigations across the molecular, cellular, and systems and behavioral level. Research in any species and at any stage of development and aging that are focused at understanding integration mechanisms underlying emergent properties of the brain and behavior are welcome.
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