Dichotomy of tyrosine hydroxylase and dopamine regulation between somatodendritic and terminal field areas of nigrostriatal and mesoaccumbens pathways.
Dichotomy of tyrosine hydroxylase and dopamine regulation between somatodendritic and terminal field areas of nigrostriatal and mesoaccumbens pathways.
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DOI：
10.1371/journal.pone.0029867
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Pruett BS
中科院分区：
文献类型：
--
作者：
Salvatore MF;Pruett BS
多巴胺调节蛋白在体树突区域的措施，往往只是作为静态指标的神经元活力，忽视了体树突多巴胺（DA）信号传导的行为和潜在的自主性之间的体树突和终端领域的隔间DA调节的可能影响。DA再摄取能力在体树突区域较少，可能在该隔室内对从头DA生物合成施加更大的负担以维持DA信号传导。因此，酪氨酸羟化酶（TH）活性的调节可能是特别重要的体树突DA信号。TH在ser 31或ser 40的磷酸化可以增加活性，但它们对体内L-DOPA生物合成的影响尚不清楚。因此，确定它们与L-DOPA组织含量的关系可以揭示DA信号正常维持的机制。在Brown-Norway Fischer 344 F1杂交大鼠中，我们定量TH磷酸化与L-DOPA积累。芳香酸脱羧酶抑制后，L-DOPA组织含量每恢复TH蛋白是最大的NAC，匹配的差异，在ser 31，但不是ser 40，磷酸化。左旋多巴每儿茶酚胺和DA周转率显着更大的SN和VTA，表明更大的依赖于从头DA生物合成。这些房室差异反映了DA调节的整体自主性，如SN和VTA中DA含量降低所示，但纹状体或NAc中的DA含量没有降低，这是由于局部输注TH抑制剂α-甲基-p-酪氨酸导致的短期DA生物合成抑制以及长期衰老过程所致。这些数据表明ser 31磷酸化在体内调节TH活性中起着重要作用，特别是在体树突区域，其可能对从头DA生物合成具有更大的依赖性。因此，在一定程度上，体树突DA释放影响行为，TH调节中脑可能是至关重要的DA生物利用度影响行为。
Measures of dopamine-regulating proteins in somatodendritic regions are often used only as static indicators of neuron viability, overlooking the possible impact of somatodendritic dopamine (DA) signaling on behavior and the potential autonomy of DA regulation between somatodendritic and terminal field compartments. DA reuptake capacity is less in somatodendritic regions, possibly placing a greater burden on de novo DA biosynthesis within this compartment to maintain DA signaling. Therefore, regulation of tyrosine hydroxylase (TH) activity may be particularly critical for somatodendritic DA signaling. Phosphorylation of TH at ser31 or ser40 can increase activity, but their impact on L-DOPA biosynthesis in vivo is unknown. Thus, determining their relationship with L-DOPA tissue content could reveal a mechanism by which DA signaling is normally maintained. In Brown-Norway Fischer 344 F1 hybrid rats, we quantified TH phosphorylation versus L-DOPA accumulation. After inhibition of aromatic acid decarboxylase, L-DOPA tissue content per recovered TH protein was greatest in NAc, matched by differences in ser31, but not ser40, phosphorylation. The L-DOPA per catecholamine and DA turnover ratios were significantly greater in SN and VTA, suggesting greater reliance on de novo DA biosynthesis therein. These compartmental differences reflected an overall autonomy of DA regulation, as seen by decreased DA content in SN and VTA, but not in striatum or NAc, following short-term DA biosynthesis inhibition from local infusion of the TH inhibitor α-methyl-p-tyrosine, as well as in the long-term process of aging. Such data suggest ser31 phosphorylation plays a significant role in regulating TH activity in vivo, particularly in somatodendritic regions, which may have a greater reliance on de novo DA biosynthesis. Thus, to the extent that somatodendritic DA release affects behavior, TH regulation in the midbrain may be critical for DA bioavailability to influence behavior.
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影响因子：
4.7
作者：
HAYCOCK, JW;WAKADE, AR
通讯作者：
WAKADE, AR
影响因子：
3
作者：
Leak, Rehana K.;Castro, Sandra L.;Zigmond, Michael J.
通讯作者：
Zigmond, Michael J.
影响因子：
2.9
作者：
Bergquist, F;Shahabi, HN;Nissbrandt, H
通讯作者：
Nissbrandt, H
DOI：
10.1073/pnas.89.6.2365
发表时间：
1992-03-15
影响因子：
11.1
作者：
HAYCOCK, JW;AHN, NG;KREBS, EG
通讯作者：
KREBS, EG
影响因子：
3.4
作者：
Andersson, Daniel R.;Nissbrandt, Hans;Bergquist, Filip
通讯作者：
Bergquist, Filip