Nigrostriatal reduction of aromatic L-amino acid decarboxylase activity in MPTP-treated squirrel monkeys: in vivo and in vitro investigations.
Nigrostriatal reduction of aromatic L-amino acid decarboxylase activity in MPTP-treated squirrel monkeys: in vivo and in vitro investigations.
复制标题
MPTP 处理的松鼠猴中芳香族 L-氨基酸脱羧酶活性的黑质纹状体降低：体内和体外研究。
DOI：
10.1046/j.1471-4159.2000.741147.x
复制
发表时间：
2000
影响因子：
4.7
通讯作者：
Barrio,JR
中科院分区：
文献类型：
--
作者：
Yee,RE;Huang,SC;Stout,DB;Irwin,I;Shoghi-Jadid,K;Togaski,DM;DeLanney,LE;Langston,JW;Satyamurthy,N;Farahani,KF;Phelps,ME;Barrio,JR
在用分级剂量的神经毒素1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）损伤的松鼠猴中，使用6-[18 F]氟-L-多巴（FDOPA），通过正电子发射断层扫描（PET）在体内检测芳香族L-氨基酸脱羧酶（AAAD）活性。在相同动物中进行尾状核、壳核、黑质和丘脑核中AAAD活性的体外生化测定，以建立体内和体外测量的直接比较。在尾状核/壳核中的体内和体外AAAD活性在用最高剂量的MPTP（2.0 mg/kg）处理的动物中显著降低。MPTP处理导致的纹状体FDOPA摄取（Ki）和脱羧速率常数（k3）值的百分比变化显示与体外测定的AAAD活性高度显著相关。然而，个体动物的脱羧酶速率在体内和体外值之间存在约10倍的差异。较低的在vivok 3测量值可能归因于几种可能性，包括运输限制限制底物的可用性AAAD内的神经元。此外，黑质中AAAD活性的降低并不与纹状体中AAAD活性的降低平行，这支持了黑质纹状体细胞变性和末端损失之间的非线性关系的概念。这项工作进一步探索了AAAD在帕金森病中的作用，这是一个比之前认为的更重要的因素。
Aromatic L‐amino acid decarboxylase (AAAD) activity was examined in vivo with positron emission tomography (PET) using 6‐[18F]fluoro‐L‐DOPA (FDOPA) in squirrel monkeys lesioned with graded doses of the neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). In vitro biochemical determinations of AAAD activity in caudate, putamen, substantia nigra, and nucleus accumbens were performed in the same animals to establish a direct comparison of in vivo and in vitro measurements. In vivo and in vitro AAAD activities in caudate/putamen were substantially reduced in animals treated with the highest dose of MPTP (2.0 mg/kg). The percent change in the striatal FDOPA uptake (Ki) and decarboxylation rate constant (k3) values resulting from MPTP treatment showed highly significant correlations with in vitro‐determined AAAD activities. However, decarboxylase rates within individual animals presented as ~ 10‐fold difference between in vivo and in vitro values. Lower in vivok3measurements may be attributed to several possibilities, including transport restrictions limiting substrate availability to AAAD within the neuron. In addition, reductions in AAAD activity in the substantia nigra did not parallel reductions in AAAD activity within the striatum, supporting the notion of a nonlinear relationship between nigrostriatal cell degeneration and terminal losses. This work further explores the role of AAAD in Parkinson's disease, a more important factor than previously thought.