LONG-TERM DIETARY ADMINISTRATION OF VALPROIC ACID DOES NOT AFFECT, WHILE RETINOIC ACID DECREASES, THE LIFESPAN OF G93A MICE, A MODEL FOR AMYOTROPHIC LATERAL SCLEROSIS
LONG-TERM DIETARY ADMINISTRATION OF VALPROIC ACID DOES NOT AFFECT, WHILE RETINOIC ACID DECREASES, THE LIFESPAN OF G93A MICE, A MODEL FOR AMYOTROPHIC LATERAL SCLEROSIS
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DOI：
10.1002/mus.21260
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发表时间：
2009-04-01
期刊：
影响因子：
3.4
通讯作者：
Contestabile, Antonio
中科院分区：
文献类型：
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作者：
Crochemore, Cristophe;Virgili, Marco;Contestabile, Antonio
携带Cu/Zn超氧化物歧化酶（G93 A）突变基因的小鼠是人类肌萎缩侧索硬化症（ALS）的良好模型。他们发展为进行性肢体瘫痪，伴随着颈脊髓和腰脊髓运动神经元的丧失，从3-3.5个月大开始，在4-5个月大时死亡。已经尝试了几种治疗方法来延迟临床症状并延长寿命，其中一些具有适度的有益效果。其中一种基于丙戊酸（VPA）长期给药的治疗导致了有争议的结果。我们在此报告，虽然通过测量脊髓中胆碱能神经元的特异性标记物评估，饮食补充高剂量VPA可减缓运动神经元死亡，但对寿命无显著影响。近年来，有研究认为视黄酸（RA）及其信号通路的缺乏可能与ALS的发生发展有关。我们报告说，长期膳食补充RA对脊髓中胆碱能标记物的减少没有影响，但它显著缩短了G93 A小鼠的寿命。
Mice bearing the mutated gene for Cu/Zn superoxide dismutase (G93A) are a good model for human amyotrophic lateral sclerosis (ALS). They develop progressive limb paralysis paralleled by loss of motor neurons of the cervical and lumbar spinal cord, which starts at 3-3.5 months of age and ends with death at 4-5 months. Several treatments have been attempted to delay clinical symptoms and to extend lifespan, and some have had modest beneficial effects. One such treatment, based on long-term administration of valproic acid (VPA), resulted in controversial results. We report here that, while dietary supplementation with high VPA dosage slows down motor neuron death, as assessed by measurement of a specific marker for cholinergic neurons in the spinal cord, it has no significant effect on lifespan. Recently, the hypothesis has been put forward that a deficiency of retinoic acid (RA) and its signaling may have a role in ALS. We report that long-term dietary supplementation with RA has no effect on the decrease of the cholinergic marker in the spinal cord, but it significantly shortens lifespan of G93A mice.