GAP-43,Netrin-1,Collapsin-1和Neuropilin-1在出生后小鼠小脑中的动态表达(英文)

Age-dependent Expression of GAP-43, Netrin-1, Collapsin-1, and Neuropilin-1 in Murine Cerebellum

GAP-43,netrin-1,collapsin-1和neuropilin-1被认为在成网络分布的神经联系中发挥重要的作用.在年幼的啮齿类动物中,小脑包含5种不同的集中分布层:白质、内颗粒细胞层(IGL)、浦肯野氏细胞层(PCL)、分子层(ML)和外颗粒细胞层(EGL).与浦肯野氏神经元在出生前产生这一点不同的是,EGL中的细胞在出生后产生,它们接受从前脑olivary核团发出的攀援纤维的主要神经投射,以及从内颗粒细胞发出的平行纤维的神经投射.这些神经投射主要在出生后的前3个星期内建立,同时还有浦肯野氏细胞的发育和成熟.而GAP-43,netrin-1,collapsin-1和neuropilin-1在出生后小脑发育的潜在作用仍然不清楚.为了更加清楚地探讨上述问题,检验了GAP-43,netrin-1,collapsin-1和neuropilin-1的mRNA与蛋白质在出生后5,10,20天和成年小鼠小脑中的表达情况.研究结果显示,这4种分子在小鼠出生后的小脑中有不同的时间和空间表达形式,这些结果与出生后发育和成年期间的轴突发生、延伸以及突触形成都有关联.通过免疫组织化学双标染色,发现小鼠出生后10天的小脑中,GAP-43阳性的浦肯野氏细胞也显示netrin-1或collapsin-1阳性,并且collapsin-1阳性的细胞也对netrin-1阳性.上述研究结果证明这4种分子可能参与了小脑的出生后发育.

GAP-43, netrin-1, collapsin-1, and neuropilin-1 have been regarded to play crucial roles in the formation of patterned neural connections. The cerebellum consists of five distinct concentric layers： white matter, internal granule layer （IGL）, Purkinje cell layer （PCL）, molecular layer （ML）, and external granule layer （EGL） in young rodents. Cells in EGL are generated after birth. In contrast Purkinje neurons are born before birth, which receive main innervations of climbing fibers from the inferior olivary nucleus and parallel fibers from the internal granule cells. These innervations are mostly established in the first three postnatal weeks, accompanying the sprouting and maturation of Purkinje cells. The potential roles of GAP-43, netrin-l, collapsin-I and neuropilin-I in the postnatal development of cerebellum remain unclear. To get insights into the above issue, the expression of GAP-43, netrin-1, collapsin-1, and neuropilin-1 mRNAs and proteins were examined in the cerebellum of mice at postnatal days （P） 5, P10, P20 and adulthood. The results showed that these four molecules were expressed in different temporal and spatial patterns in the postnatal cerebellum of mice, which was in match with axonal synaptogenesis, elongation and synapse formation during postnatal development and adulthood. By using double immunohistochemistry, it was found that the Purkinje cells stained for GAP-43 were also positive for either netrin-1 or collapsin-1 at P10, and cells stained for collapsin-1 were also positive for netrin-1 or neuropilin-1. It was suggested that the four molecules are involved in the postnatal development of cerebellum.