Development of brainstem 5-HT1A receptor-binding sites in serotonin-deficient mice.

Development of brainstem 5-HT1A receptor-binding sites in serotonin-deficient mice.
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DOI:
10.1111/jnc.12311
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发表时间:
2013-09
影响因子:
4.7
通讯作者:
Commons KG
Commons KG
中科院分区:
医学2区
文献类型:
--
作者:
Massey CA;Kim G;Corcoran AE;Haynes RL;Paterson DS;Cummings KJ;Dymecki SM;Richerson GB;Nattie EE;Kinney HC;Commons KG

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婴儿猝死综合征(SIDS)与脑干5-羟色胺(5-HT)和5-HT 1A受体结合减少有关,但这些发现是否以及如何联系尚不清楚。在这项研究中,我们使用定量组织放射自显影,以确定是否出生后的发展脑干5-HT 1A受体是改变在两个小鼠模型,其中5-HT神经元的发展是有缺陷的,Lmx 1bf/f/p,和Pet-1-/-小鼠。在5-HT源核(自身受体)和接受5-HT神经支配(异源受体)的部位检查5-HT 1A受体激动剂结合部位。在对照组小鼠出生后第3天(P)和第10天之间,5-HT 1A受体结合在几个脑干部位增加;到P25,有区域特异性的增加和减少,改善了整体结合模式。在Lmx 1bf/f/p和Pet-1-/-小鼠中,5-HT 1A-自身受体结合在P3时显著低于对照小鼠,并在P10和P25时保持较低水平。相比之下,5-HT 1A异源受体水平在对照组和5-HT缺陷小鼠之间相当。这些数据定义了出生后小鼠脑干中5-HT 1A受体结合的发育。此外,数据表明,在SIDS中检测到的5-HT 1A异源受体缺陷不是5-HT神经元功能障碍的直接后果,也不是脑5-HT水平降低的直接后果。
The sudden infant death syndrome (SIDS) is associated with a reduction in brainstem serotonin (5-hydroxytryptamine, 5-HT) and 5-HT1A receptor binding, yet it is unknown if and how these findings are linked. In this study, we used quantitative tissue autoradiography to determine if postnatal development of brainstem 5-HT1A receptors is altered in two mouse models where the development of 5-HT neurons is defective, the Lmx1bf/f/p, and the Pet-1-/- mouse. 5-HT1A receptor agonist-binding sites were examined in both 5-HT-source nuclei (autoreceptors) and in sites that receive 5-HT innervation (heteroreceptors). In control mice between postnatal day (P) 3 and 10, 5-HT1A receptor binding increased in several brainstem sites; by P25, there were region-specific increases and decreases, refining the overall binding pattern. In the Lmx1bf/f/p and Pet-1-/- mice, 5-HT1A-autoreceptor binding was significantly lower than in control mice at P3, and remained low at P10 and P25. In contrast, 5-HT1A heteroreceptor levels were comparable between control and 5-HT-deficient mice. These data define the postnatal development of 5-HT1A receptor binding in the mouse brainstem. Furthermore the data suggest that 5-HT1A heteroreceptor deficits detected in SIDS are not a direct consequence of a 5-HT neuron dysfunction nor reduced brain 5-HT levels.
DOI: 10.1523/jneurosci.1963-09.2009
发表时间: 2009-08-19
期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
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