Developmental Changes of Glutamate and GABA Receptor Densities in Wistar Rats
Developmental Changes of Glutamate and GABA Receptor Densities in Wistar Rats
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DOI：
10.3389/fnana.2019.00100
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发表时间：
2019-12-20
影响因子：
2.9
通讯作者：
Amunts, Katrin
中科院分区：
文献类型：
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作者：
Behuet, Sabrina;Cremer, Jennifer Nadine;Amunts, Katrin
神经递质及其受体是信号转导的关键分子，在出生前后的发育过程中会发生各种变化。以前的研究在神经递质和神经递质受体亚单位的表达水平上解决了个体发育。然而，受体密度的发育变化到今天还没有得到很好的理解。在这里，我们分析了兴奋性谷氨酸和抑制性γ-氨基丁酸（GABA）受体在大鼠大脑的相邻部分的定量体外受体放射自显影的发展变化。使用特异性高亲和力配体研究了离子型谷氨酸能受体α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）、红藻氨酸盐和N-甲基-D-天冬氨酸（NMDA）以及离子型GABA（A）和代谢型GABA（B）受体的受体密度。对于每个受体结合位点，在研究的感兴趣区域[嗅球、纹状体、海马和小脑]和发育阶段[出生后（P）0、10、20、30和90天]中证明了显著的密度差异。特别是，我们发现，多巴胺能和GABA能受体密度已经存在于P0和P10之间的所有感兴趣的区域，这可能表明这些受体与大脑发育的早期相关性。在海马中的海马受体密度的瞬时增加，表明它们可能参与突触可塑性。我们证明了从P30到P90纹状体和海马中NMDA受体密度的下降，这可能是由于突触消除，这是一个重新定义出生后大脑中神经元网络的过程。此外，GABA（A）受体密度从P10到P20的最高增加与从兴奋性到抑制性GABA传递的发育转变相一致。此外，小脑中GABA（A）受体密度从P10到P20的增加对应于功能性GABA能突触形成的时间点。两者合计，目前的数据显示，在出生后大鼠脑发育过程中，谷氨酸和GABA受体密度的差异变化，这可能有助于其特定的功能在个体发育过程中，从而提供了更深入的了解脑个体发育和受体功能。
Neurotransmitters and their receptors are key molecules of signal transduction and subject to various changes during pre- and postnatal development. Previous studies addressed ontogeny at the level of neurotransmitters and expression of neurotransmitter receptor subunits. However, developmental changes in receptor densities to this day are not well understood. Here, we analyzed developmental changes in excitatory glutamate and inhibitory gamma-aminobutyric acid (GABA) receptors in adjacent sections of the rat brain by means of quantitative in vitro receptor autoradiography. Receptor densities of the ionotropic glutamatergic receptors alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate and N-methyl-D-aspartate (NMDA) as well as of the ionotropic GABA(A) and metabotropic GABA(B) receptors were investigated using specific high-affinity ligands. For each receptor binding site, significant density differences were demonstrated in the investigated regions of interest [olfactory bulb, striatum, hippocampus, and cerebellum] and developmental stages [postnatal day (P) 0, 10, 20, 30 and 90]. In particular, we showed that the glutamatergic and GABAergic receptor densities were already present between P0 and P10 in all regions of interest, which may indicate the early relevance of these receptors for brain development. A transient increase of glutamatergic receptor densities in the hippocampus was found, indicating their possible involvement in synaptic plasticity. We demonstrated a decline of NMDA receptor densities in the striatum and hippocampus from P30 to P90, which could be due to synapse elimination, a process that redefines neuronal networks in postnatal brains. Furthermore, the highest increase in GABA(A) receptor densities from P10 to P20 coincides with the developmental shift from excitatory to inhibitory GABA transmission. Moreover, the increase from P10 to P20 in GABA(A) receptor densities in the cerebellum corresponds to a point in time when functional GABAergic synapses are formed. Taken together, the present data reveal differential changes in glutamate and GABA receptor densities during postnatal rat brain development, which may contribute to their specific functions during ontogenesis, thus providing a deeper understanding of brain ontogenesis and receptor function.