Fonta Caroline, Négyessy László, Renaud Luc, Barone Pascal
Cerveau et Cognition, CNRS-UMR 5549 Université P. Sabatier, Toulouse, France.
Cereb Cortex. 2004 Jun;14(6):595-609. doi: 10.1093/cercor/bhh021. Epub 2004 Mar 28.
The ubiquitous enzyme TNAP (tissue non-specific alkaline phosphatase) is found in numerous tissues such as liver, kidney and bone, but little attention has been paid to its expression and role in the brain. Observations in TNAP-KO mice, which analyzed the role of this enzyme in osteogenesis, had suggested that TNAP might be involved in GABA neurotransmission. Apart from its presence in endothelial cells, here we show a specific and strong alkaline phosphatase (AP) activity in the neuropile, matching the pattern of thalamo-cortical innervation in layer 4 of the primate sensory cortices (visual, auditory and somatosensory). Such a pattern is also evident in rodents and carnivores, making AP a powerful marker of primary sensory areas. Remarkably, AP activity is regulated by sensory experience as demonstrated by monocular deprivation paradigms in monkeys. The areal and laminar distribution of AP activity matches that of the GAD(65), the GABA synthesizing enzyme found in presynatic terminals. As our electron microscopic investigations indicate that AP is found at the neuronal membranes and in synaptic contacts, it is proposed that the neuronal AP isoform (NAP), may be a key enzyme in regulating neurotransmission and could therefore play an important role in developmental plasticity and activity-dependent cortical functions.
普遍存在的酶TNAP（组织非特异性碱性磷酸酶）存在于许多组织中，如肝脏、肾脏和骨骼，但人们对其在大脑中的表达和作用关注甚少。对TNAP基因敲除小鼠的观察分析了这种酶在骨生成中的作用，结果表明TNAP可能参与γ-氨基丁酸（GABA）神经传递。除了在内皮细胞中存在外，我们在此展示了神经毡中特异性且强烈的碱性磷酸酶（AP）活性，这与灵长类感觉皮层（视觉、听觉和躯体感觉）第4层的丘脑-皮质神经支配模式相匹配。这种模式在啮齿动物和食肉动物中也很明显，使得AP成为初级感觉区域的有力标记物。值得注意的是，如猴子的单眼剥夺实验所示，AP活性受感觉经验调节。AP活性的区域和层状分布与GAD（65）（一种存在于突触前终末的GABA合成酶）的分布相匹配。由于我们的电子显微镜研究表明AP存在于神经元膜和突触接触中，因此有人提出神经元AP同工型（NAP）可能是调节神经传递的关键酶，因此可能在发育可塑性和依赖活动的皮层功能中发挥重要作用。
