Winzer-Serhan Ursula H, Leslie Frances M
Department of Medical Pharmacology and Toxicology, Health Science Center, Texas A and M University System, College Station, Texas 77843, USA.
J Comp Neurol. 2005 Jan 3;481(1):19-30. doi: 10.1002/cne.20357.
Nicotinic acetylcholine receptors (nAChRs) are ligand-gated pentameric cation channels of alpha and beta subunits. The alpha5 subunit, when added to heteromeric complexes, alters pharmacological and physiological properties of nAChRs, which may be important during development. Here we have evaluated the pre- and postnatal expression of alpha5 subunit mRNA in rat cortex and hippocampus using highly sensitive in situ hybridization. In the cortex, alpha5 mRNA was detected in the subplate, claustrum, and endopiriform nucleus at embryonic day 18 (E18), areas with sustained expression into adulthood. Transient cortical expression was detected in numerous cells, scattered mainly in layers V and II/III, during the first 2 postnatal weeks. In the hippocampus, alpha5 transcripts first appeared in the CA1 region at E18. During postnatal development, increased hybridization signal was detected in CA1 and CA3 pyramidal neurons and granule cells of the dentate gyrus, which strongly contrasted with the low levels in the adult. Interneurons in CA1/CA3 stratum radiatum and moleculare, and in the hilus region of the dentate gyrus, strongly expressed alpha5 mRNA in postnatal and adult animals. With double in situ hybridization, co-expression of alpha5 and alpha7 mRNAs was detected in a subpopulation of hippocampal interneurons. In contrast, in the subiculum, numerous cells exhibited strong hybridization signal for alpha5 and alpha7 mRNAs, but co-expression was rarely detected. In conclusion, similar to other nAChR subunits, there is transient expression of alpha5 mRNA during cortical and hippocampal development. This expression pattern places nicotinic receptors containing the alpha5 subunit in a position to regulate glutamatergic and GABAergic transmission during the postnatal period.
烟碱型乙酰胆碱受体(nAChRs)是由α和β亚基组成的配体门控五聚体阳离子通道。α5亚基添加到异聚复合物中时,会改变nAChRs的药理学和生理学特性,这在发育过程中可能很重要。在这里,我们使用高灵敏度原位杂交技术评估了大鼠皮质和海马中α5亚基mRNA在产前和产后的表达情况。在皮质中,胚胎第18天(E18)时,在板下层、屏状核和内梨状核中检测到α5 mRNA,这些区域持续表达至成年期。在出生后的前两周,在许多细胞中检测到短暂的皮质表达,这些细胞主要分散在V层和II/III层。在海马中,α5转录本在E18时首次出现在CA1区域。在出生后的发育过程中,在CA1和CA3锥体神经元以及齿状回的颗粒细胞中检测到杂交信号增加,这与成年期的低水平形成强烈对比。CA1/CA3辐射层和分子层以及齿状回门区的中间神经元在出生后和成年动物中强烈表达α5 mRNA。通过双重原位杂交,在海马中间神经元的一个亚群中检测到α5和α7 mRNA的共表达。相比之下,在海马下托中,许多细胞对α5和α7 mRNA表现出强烈的杂交信号,但很少检测到共表达。总之,与其他nAChR亚基类似,α5 mRNA在皮质和海马发育过程中存在短暂表达。这种表达模式使含有α5亚基的烟碱型受体能够在出生后调节谷氨酸能和GABA能传递。