Yoshimura M, Saji M
Division of Child Neurology, Tottori University Faculty of Medicine, Yonago, Japan.
Brain Res Dev Brain Res. 1998 Jan 14;105(1):25-33.
In adult rats, combined lesions of the striatum and globus pallidus (GP) cause transsynaptic cell death of neurons in the substantia nigra pars reticulata (SNr) which becomes apparent 1-2 weeks after the lesions. This delayed cell death of SNr neurons has been explained to be caused by over-excitation of SNr neurons which results from an imbalance between excitatory and inhibitory inputs due to two simultaneous events: acceleration of the excitatory input from the disinhibited subthalamic nucleus (STN) and deprivation of the inhibitory input from the striatum. To examine whether the transsynaptic neuronal death in SNr is caused by the same lesions in developing rats, we destroyed the striatum and GP in rats on postnatal days 10 (P10), P15, P20, P25, P30, P35 and P60 by injecting ibotenic acid. We found that cell death did not occur in SNr neurons in rats younger than P20 and that Fos expression induced in STN neurons after these striatopallidal lesions in P10 and P20 rats was lower than that in P30 or P60 rats. These findings suggest that excitation of STN neurons is not enough to cause cell death of SNr neurons in rats younger than P20. Immature functional connection between the cerebral cortex and STN in the early developing animals may contribute to the resistivity of SNr neurons to transsynaptic delayed cell death.
在成年大鼠中，纹状体和苍白球（GP）的联合损伤会导致黑质网状部（SNr）神经元发生跨突触细胞死亡，这种死亡在损伤后1 - 2周变得明显。SNr神经元的这种延迟性细胞死亡被解释为是由于SNr神经元过度兴奋所致，而过度兴奋是由两个同时发生的事件导致的兴奋性和抑制性输入失衡引起的：来自解除抑制的丘脑底核（STN）的兴奋性输入加速，以及来自纹状体的抑制性输入缺失。为了研究SNr中的跨突触神经元死亡是否由发育中大鼠的相同损伤引起，我们在出生后第10天（P10）、P15、P20、P25、P30、P35和P60的大鼠中通过注射鹅膏蕈氨酸破坏纹状体和GP。我们发现，P20以下的大鼠SNr神经元中未发生细胞死亡，并且在P10和P20大鼠的这些纹状体苍白球损伤后，STN神经元中诱导的Fos表达低于P30或P60大鼠。这些发现表明，STN神经元的兴奋不足以导致P20以下大鼠的SNr神经元细胞死亡。早期发育动物大脑皮层与STN之间未成熟的功能连接可能有助于SNr神经元对跨突触延迟性细胞死亡的抵抗力。
