Deafferentation-induced apoptosis of neurons in thalamic somatosensory nuclei of the newborn rat: critical period and rescue from cell death by peripherally applied neurotrophins
Deafferentation-induced apoptosis of neurons in thalamic somatosensory nuclei of the newborn rat: critical period and rescue from cell death by peripherally applied neurotrophins
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DOI：
10.1046/j.1460-9568.2000.00119.x
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发表时间：
2000-07-01
影响因子：
3.4
通讯作者：
Keller, F
中科院分区：
文献类型：
--
作者：
Baldi, A;Calia, E;Keller, F
本研究用末端转移酶介导的脱氧尿嘧啶核苷-生物素缺口末端标记法(TUNEL)和电子显微镜证实，新生大鼠(P0)一侧眶下神经(ION)切断可诱导对侧丘脑腹基底核(VB)复合体细胞凋亡。双标记实验用标记的微球逆行转运注射到桶状皮质，然后进行TUNEL染色，结果表明TUNEL阳性细胞是丘脑皮质神经元。TUNEL阳性细胞数在损伤后24 h开始增加，48 h进一步增加，120 h后降至对照组水平，损伤诱导的VB复合体细胞凋亡在P4时不明显，在P7时消失。这一时间进程与桶状皮质损伤诱导可塑性的关键期非常吻合。神经生长因子(NGF)或脑源性神经营养因子(BDNF)单独或联合应用于离子残端，可部分挽救丘脑神经元的凋亡。在P0行离子切割术的P7动物VB复合体中的细胞总数证实了BDNF和NGF的抢救作用。阻断离子内轴突运输的作用类似于离子段的作用。这些数据表明，在神经元连接微调期间，躯体感觉系统中的高阶神经元的生存需要来自外周的促存活信号，可能是神经营养素。我们还提出，新生大鼠三叉神经系统顺行性跨神经元变性可能是研究体内细胞程序性死亡途径的一种新的动物模型。
This study shows that unilateral transection of the infraorbital nerve (ION) in newborn (P0) rats induces apoptosis in the contralateral ventrobasal thalamic (VB) complex, as evidenced by terminal transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) and electron miscroscopy. Double-labelling experiments using retrograde transport of labelled microspheres injected into the barrel cortex, followed by TUNEL staining, show that TUNEL-positive cells are thalamocortical neurons. The number of TUNEL-positive cells had begun to increase by 24 h postlesion, increased further 48 h after nerve section, and decreased to control levels after 120 h. Lesion-induced apoptosis in the VB complex is less pronounced if ION section is performed at P4, and disappears if the lesion is performed at P7. This time course closely matches the critical period of lesion-induced plasticity in the barrel cortex. Nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF), applied on the ION stump alone or in combination, are able to partially rescue thalamic neurons from apoptosis. Total cell counts in the VB complex of P7 animals that underwent ION section at P0 confirm the rescuing effect of BDNF and NGF. Blockade of axonal transport in the ION mimics the effect of ION section. These data suggest that survival-promoting signals from the periphery, maybe neurotrophins, are required for the survival of higher-order neurons in the somatosensory system during the period of fine-tuning of neuronal connections. We also propose that anterograde transneuronal degeneration in the neonatal rat trigeminal system may represent a new animal model for studying the pathways of programmed cell death in vivo.