Singular subsets of locus coeruleus neurons may recover tyrosine hydroxylase phenotype transiently expressed during development
Singular subsets of locus coeruleus neurons may recover tyrosine hydroxylase phenotype transiently expressed during development
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DOI：
10.1016/s0169-328x(00)00007-3
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发表时间：
2000-03-29
期刊：
影响因子：
--
通讯作者：
Weissmann, D
中科院分区：
文献类型：
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作者：
Bezin, L;Marcel, D;Weissmann, D
表达酪氨酸羟化酶 (TH) 的神经元的数量似乎是在去甲肾上腺素能脑桥蓝核 (LC) 内的基础条件下精确确定的。然而，在单次施用 RU 24722（LC 特异性 TH 表达的有效诱导剂）后，在成年大鼠 LC 中观察到表现出 TH 表型的额外神经元。治疗后获得 TH 表型的神经元具有与神经元相似的拓扑定位，在出生后发育期间短暂表达 TH，并在出生后第三周失去 TH 表型。发育过程中 LC 神经元单一亚群的 TH 表型波动可能在成人中选择性恢复的想法特别令人感兴趣。本研究试图确定在出生后第三周内 TH 表达受到抑制的细胞是否与成人中对 RU 24722 治疗反应而表现出 TH 表型的细胞相对应。我们首先验证了在第 13 天至第 30 天期间，LC 中没有发生大量细胞死亡。然后，我们观察到与永久表达 TH 的细胞相比，两个细胞群都表现出相同的 TH-mRNA 稳态浓度变化。最后，我们证明了表达同源结构域转录因子 Phox2a 的 TH 阴性神经元的存在，该因子对去甲肾上腺素表型的测定具有特异性，进一步证明在基础条件下成年大鼠 LC 中存在“静息去甲肾上腺素能”神经元。当经典去甲肾上腺素能 LC 神经元受损时，这些神经元为去甲肾上腺素能功能的获得提供了有趣的前景。 (C) 2000 Elsevier Science B.V. 保留所有权利。
The number of tyrosine hydroxylase (TH)-expressing neurons appears to be precisely determined in basal conditions within the noradrenergic pontine nucleus locus coeruleus (LC). However, additional neurons exhibiting TH phenotype have been observed in the adult rat LC following a single administration of RU 24722, a potent inducer of TH expression specific to the LC. The neurons acquiring TH phenotype following treatment had a topographical localization similar to that of the neurons, which transiently expressed TH during postnatal development and lost TH phenotype during the third postnatal week. The idea that the fluctuation of TH phenotype in singular subsets of LC neurons during development may be selectively restored in adults is of particular interest. The present study attempted to determine whether the cells in which TH expression was repressed during the third postnatal week could correspond to those which exhibited TH phenotype in response to RU 24722 treatment in adults. We first verified that no massive cell death occurred in the LC during the period ranging from days 13 to 30. Then, we observed that both cell populations exhibited the same altered steady-state concentration of TH-mRNA as compared to cells that permanently expressed TH. Finally, we demonstrated the presence of TH-negative neurons expressing the homeodomain transcription factor Phox2a, specific for the determination of noradrenergic phenotype, providing further evidence that "resting-noradrenergic" neurons exist in the adult rat LC under basal conditions. These neurons provide interesting prospective for gain of noradrenergic function when classical noradrenergic LC neurons are impaired. (C) 2000 Elsevier Science B.V. All rights reserved.