Hansson S R, Cabrera-Vera T M, Hoffman B J
Unit on Molecular Pharmacology, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, MD 20892, USA.
Brain Res Dev Brain Res. 1998 Dec 7;111(2):305-14. doi: 10.1016/s0165-3806(98)00148-5.
The serotonin transporter MRNA has been found throughout the trigeminal sensory system late in gestation and during early postnatal development, a period known to be critical for maturation of the sensory circuitry. The purpose of the present study was to determine whether sensory denervation in newborn rat pups would alter either the density or pattern of expression of the 5-HT transporter (5-HTT) within the trigeminal system. We combined autoradiographic localization of 5-HT transporters and in situ hybridization techniques to visualize both the transporter protein and mRNA in thalamic sensory neurons and in the somatosensory cortex following unilateral infraorbital nerve transection at postnatal day 1. For comparative purposes, similar measurements were conducted in thalamic visual neurons as well as in the visual cortex. Lesion of the infraorbital nerve decreased the [3H]citalopram labelling of 5-HT transporters in the ventral basal and ventral medial areas of the thalamus contralateral to the lesion, while labelling of 5-HT transporters was decreased in both contralateral and ipsilateral sides of the lateral genicuate (visual thalamus). Citalopram labelling of 5-HT transporters was not significantly altered in somatosensory or in cingulate cortex, however a significant decrease was observed in the visual cortex. In contrast, there were no obvious changes in the intensity of the 5-HT mRNA hybridization signal in sensory or visual thalamic areas. Given that the serotonin transporter regulates extracellular concentrations of 5-HT, the present data suggest that altered peripheral innervation and thereby altered sensory inputs to the thalamus during fetal development can potentially influence 5-HT transporter densities and thus, may influence extracellular levels of 5-HT in thalamus and cortex during a critical period of synapse formation. In turn, modulation of 5-HT transporter levels may influence extracellular concentrations of 5-HT in thalamus and cortex during a critical period of synapse formation.
在妊娠后期及出生后早期发育阶段,血清素转运体信使核糖核酸(mRNA)在整个三叉神经感觉系统中均有发现,这一时期对于感觉神经回路的成熟至关重要。本研究的目的是确定新生大鼠幼崽的感觉去神经支配是否会改变三叉神经系统中5-羟色胺转运体(5-HTT)的表达密度或模式。我们将5-HT转运体的放射自显影定位与原位杂交技术相结合,以观察出生后第1天单侧眶下神经横断后丘脑感觉神经元和体感皮层中的转运体蛋白和mRNA。为作比较,我们在丘脑视觉神经元以及视觉皮层中进行了类似测量。眶下神经损伤降低了损伤对侧丘脑腹侧基底和腹内侧区域5-HT转运体的[3H]西酞普兰标记,而外侧膝状体(视觉丘脑)的对侧和同侧5-HT转运体的标记均减少。5-HT转运体的西酞普兰标记在体感皮层或扣带回皮层中无显著改变,但在视觉皮层中观察到显著降低。相比之下,感觉或视觉丘脑区域中5-HT mRNA杂交信号的强度没有明显变化。鉴于血清素转运体调节细胞外5-HT的浓度,目前的数据表明,胎儿发育期间外周神经支配的改变以及由此改变的丘脑感觉输入可能会潜在影响5-HT转运体密度,进而可能在突触形成的关键时期影响丘脑和皮层中5-HT的细胞外水平。反过来,在突触形成的关键时期,5-HT转运体水平的调节可能会影响丘脑和皮层中5-HT的细胞外浓度。