Holmer Haley K, Keyghobadi Modjgan, Moore Cynthia, Menashe Rachelle A, Meshul Charles K
Research Services, Neurocytology Lab, V.A. Medical Center, Portland, Oregon 97239, USA.
Synapse. 2005 Aug;57(2):100-12. doi: 10.1002/syn.20163.
One month following subchronic treatment with the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg/kg/d x 7 days), there is a decrease in the extracellular level of striatal glutamate. It has been reported that following dietary restriction (DR) (fed on alternate days) of C57BL/6 mice, MPTP administration resulted in a reduction in the loss of tyrosine hydroxylase-positive neurons within the substantia nigra pars compacta (SN-PC) compared to the ad libitum (AL)-fed MPTP-treated mice. However, there have been no reports of whether the MPTP-induced alterations in brain neurochemistry or morphology can be similarly attenuated by DR if initiated after administration of the toxin. In the MPTP/AL group there is a decrease in the extracellular level of striatal glutamate compared to the Vehicle/AL group. However, 21 days of DR starting 1 day after the last subchronic dose of MPTP results in a reversal in the extracellular level of striatal glutamate compared to the MPTP/AL group. DR alone resulted in a decrease in extracellular striatal glutamate. There was no change in the relative density of the glutamate transporter, GLT-1, within the striatum or SN-PC between any of the groups, suggesting that the alterations in striatal extracellular glutamate were not due to a change in this specific transporter. There was an increase in the density of nerve terminal glutamate immunolabeling in the MPTP/AL and MPTP/DR groups compared to the Vehicle/AL group. There was a similar decrease in the relative density of tyrosine hydroxylase immunolabeling within the striatum and the SN-PC in both the MPTP/AL and MPTP/DR groups compared to the Vehicle/AL group. Since a decrease in the activity of the corticostriatal glutamate pathway has been reported in both Parkinson's disease and in animal models of nigrostriatal loss, these data suggest that DR initiated after the partial loss of striatal dopamine appears to reverse the decrease in striatal glutamate.
在用神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）（30毫克/千克/天，共7天）进行亚慢性治疗一个月后，纹状体谷氨酸的细胞外水平降低。据报道，对C57BL/6小鼠进行隔日饮食限制（DR）后，与自由采食（AL）的MPTP处理小鼠相比，给予MPTP导致黑质致密部（SN-PC）中酪氨酸羟化酶阳性神经元的损失减少。然而，尚无关于在给予毒素后开始的DR是否能类似地减轻MPTP诱导的脑内神经化学或形态学改变的报道。与溶剂/AL组相比，MPTP/AL组纹状体谷氨酸的细胞外水平降低。然而，在最后一次亚慢性剂量的MPTP给药后1天开始的21天DR导致与MPTP/AL组相比纹状体谷氨酸的细胞外水平逆转。单独的DR导致纹状体细胞外谷氨酸减少。任何组之间纹状体或SN-PC内谷氨酸转运体GLT-1的相对密度均无变化，这表明纹状体细胞外谷氨酸的改变不是由于该特定转运体的变化所致。与溶剂/AL组相比，MPTP/AL组和MPTP/DR组中神经末梢谷氨酸免疫标记的密度增加。与溶剂/AL组相比，MPTP/AL组和MPTP/DR组纹状体和SN-PC内酪氨酸羟化酶免疫标记的相对密度均有类似程度的降低。由于在帕金森病和黑质纹状体损伤的动物模型中均报道了皮质纹状体谷氨酸途径的活性降低，这些数据表明在纹状体多巴胺部分丧失后开始的DR似乎能逆转纹状体谷氨酸的降低
