Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
J Oral Pathol Med. 2012 Apr;41(4):354-60. doi: 10.1111/j.1600-0714.2011.01109.x. Epub 2011 Nov 16.
We previously developed a rat trigeminal motor neuron axotomy model involving masseter and temporal muscle resection to study pathological changes of the central nucleus after peripheral nerve injury caused by oral surgery. Because motor neurons are reported to be more vulnerable to axotomy in mice than rats, we compared the degeneration process of the trigeminal motor nucleus in the rat model with a similar mouse model.
We removed masseter and temporal muscles of adult mice or rats. Animals were sacrificed at 3, 7, 14, 28, 42, and 56 days post-operation, and the trigeminal motor nuclei were histologically analyzed.
Size reduction, but no neuronal loss, was seen in the trigeminal motor nuclei in both mice and rats. Time-dependent Noxa expression, starting at 1 week post-operation (wpo), was seen in the mouse model. By 8 wpo, mice expressed a higher level of Noxa than rats. Additionally, we noted persistent expression of cleaved caspase-3 in mice but not in rats. Conversely, apoptosis-inducing factor (AIF), which executes DNA fragmentation in the nucleus, was not translocated to the nucleus in either model.
Our findings indicate differential activation of motor neuron apoptosis pathways after axotomy in mice and rats. Lack of activation of caspase-independent pathways and distal end denervation in our model might be related to the survival of motor neurons after axonal injury. These findings could be relevant to future neuroprotective strategies for peripheral nerve injury caused by oral surgeries.
我们之前开发了一种涉及咬肌和颞肌切除的大鼠三叉神经运动神经元切断模型,以研究口腔手术后周围神经损伤对中枢核的病理变化。因为据报道运动神经元在小鼠中比在大鼠中更容易受到轴突切断的影响,所以我们比较了大鼠模型和类似的小鼠模型中三叉神经运动核的退化过程。
我们切除成年小鼠或大鼠的咬肌和颞肌。动物在手术后 3、7、14、28、42 和 56 天被处死,并对三叉神经运动核进行组织学分析。
在小鼠和大鼠中,三叉神经运动核均出现体积缩小,但神经元未丢失。在小鼠模型中,从术后 1 周(wpo)开始可见 Noxa 表达增加。到 8 wpo 时,小鼠表达的 Noxa 水平高于大鼠。此外,我们还注意到在小鼠中持续表达裂解的 caspase-3,但在大鼠中没有。相反,在两种模型中,执行核内 DNA 片段化的凋亡诱导因子(AIF)都没有转移到核内。
我们的发现表明,在小鼠和大鼠中,轴突切断后运动神经元凋亡途径的激活存在差异。我们的模型中 caspase 非依赖性途径和远端去神经支配的缺乏可能与轴突损伤后运动神经元的存活有关。这些发现可能与未来针对口腔手术引起的周围神经损伤的神经保护策略有关。