Restricted neuronal expression of ubiquitous mitochondrial creatine kinase: Changing patterns in development and with increased activity
Restricted neuronal expression of ubiquitous mitochondrial creatine kinase: Changing patterns in development and with increased activity
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DOI：
10.1023/a:1022409101641
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发表时间：
2003-02-01
影响因子：
4.3
通讯作者：
Khuchua, Z
中科院分区：
文献类型：
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作者：
Boero, J;Qin, W;Khuchua, Z
虽然ATP的消耗随着神经活动的增加而增加，并被磷酸肌酸(PCR)缓冲，但目前尚不清楚无所不在的线粒体肌酸激酶(UMtCK)合成的PCR是否支持所有神经元的能量代谢。为了探索神经元中uMtCK的表达受活动和发育过程的调控的可能性，我们使用免疫细胞化学方法检测了含有uMtCK的线粒体。在成人脑内，神经元亚群包括Va层锥体细胞、丘脑大部分核团、小脑浦肯野细胞、嗅觉二尖瓣细胞和海马间神经元强烈表达uMtCK。UMtCK在出生时由一大群神经元瞬时表达。出生时各皮层神经元均表达uMtCK(P0)，但P12仅限于Va层。UMtCK在出生时在小脑浦肯野细胞中检测到，但仅在出生后5天观察到树突，并在出生后14天达到最大。出生时，海马CA1和CA3锥体神经元含有uMtCK阳性线粒体，但这种模式逐渐局限于中间神经元。癫痫发作诱导皮质II-III层和CA1层锥体神经元uMtCK表达。在大脑皮层，阻断癫痫发作可阻止uMtCK的诱导，而在CA1区则不然。这些发现支持uMtCK在神经元中的表达是(1)出生后发育调节的，(2)在成人大脑中受结构性限制的，(3)受皮质和海马区活动调节的。这意味着，线粒体的聚合酶链式反应的合成仅限于那些表达uMtCK的神经元，并可能有助于在能量需求增加的时期保护这些细胞。
Whereas ATP consumption increases with neural activity and is buffered by phosphocreatine (PCr), it is not known whether PCr synthesis by ubiquitous mitochondrial creatine kinase (uMtCK) supports energy metabolism in all neurons. To explore the possibility that uMtCK expression in neurons is modulated by activity and during development, we used immunocytochemistry to detect uMtCK-containing mitochondria. In the adult brain, subsets of neurons including layer Va pyramidal cells, most thalamic nuclei, cerebellar Purkinje cells, olfactory mitral cells and hippocampal interneurons strongly express uMtCK. uMtCK is transiently expressed by a larger group of neurons at birth. Neurons in all cortical layers express uMtCK at birth (P0), but uMtCK is restricted to layer Va by P12. uMtCK is detected in cerebellar Purkinje cells at birth, but localization to dendrites is only observed after P5 and is maximal on P14. Hippocampal CA1 and CA3 pyramidal neurons contain uMtCK-positive mitochondria at birth, but this pattern becomes progressively restricted to interneurons. Seizures induced uMtCK expression in cortical layers II-III and CA1 pyramidal neurons. In the cortex, but not in CA1, blockade of seizures prevented the induction of uMtCK. These findings support the concept that uMtCK expression in neurons is (1) developmentally regulated in post-natal life, (2) constitutively restricted in the adult brain, and (3) regulated by activity in the cortex and hippocampus. This implies that mitochondrial synthesis of PCr is restricted to those neurons that express uMtCK and may contribute to protect these cells during periods of increased energy demands.