Collin Tove, Arvidsson Andreas, Kokaia Zaal, Lindvall Olle
Laboratory of Neurogenesis and Cell Therapy, Section of Restorative Neurology, Wallenberg Neuroscience Center, BMC A11, SE-221 84 Lund, Sweden.
Exp Neurol. 2005 Sep;195(1):71-80. doi: 10.1016/j.expneurol.2005.03.017.
Recent findings in adult rodents have provided evidence for the formation of new striatal neurons from subventricular zone (SVZ) precursors following stroke. Little is known about which factors determine the magnitude of striatal neurogenesis in the damaged brain. Here we studied striatal neurogenesis following an excitotoxic lesion to the adult rat striatum induced by intrastriatal quinolinic acid (QA) infusion. New cells were labeled with the thymidine-analogue 5-bromo-2'-deoxyuridine (BrdU) and their identity was determined immunocytochemically with various phenotypic markers. The unilateral lesion gave rise to increased cell proliferation mainly in the ipsilateral SVZ. At 2 weeks following the insult, there was a pronounced increase of the number of new neurons co-expressing BrdU and a marker of migrating neuroblasts, doublecortin, in the ipsilateral striatum, particularly its non-damaged medial parts. About 80% of the new neurons survived up to 6 weeks, when they expressed the mature neuronal marker NeuN and were preferentially located in the outer parts of the damaged area. Lesion-generated neurons expressed phenotypic markers of striatal medium spiny neurons (DARPP-32) and interneurons (parvalbumin or neuropeptide Y). The magnitude of neurogenesis correlated to the size of the striatal damage. Our data show for the first time that an excitotoxic lesion to the striatum can trigger the formation of new striatal neurons with phenotypes of both projection neurons and interneurons.
近期在成年啮齿动物中的研究发现，中风后室下区（SVZ）前体细胞可形成新的纹状体神经元。关于哪些因素决定受损大脑中纹状体神经发生的程度，目前知之甚少。在此，我们研究了成年大鼠纹状体内注射喹啉酸（QA）诱发兴奋性毒性损伤后纹状体的神经发生情况。用胸苷类似物5-溴-2'-脱氧尿苷（BrdU）标记新细胞，并通过各种表型标志物进行免疫细胞化学鉴定其身份。单侧损伤主要导致同侧SVZ细胞增殖增加。损伤后2周，同侧纹状体中同时表达BrdU和迁移神经母细胞标志物双皮质素的新神经元数量显著增加，尤其是在其未受损的内侧部分。约80%的新神经元存活至6周，此时它们表达成熟神经元标志物NeuN，并优先位于受损区域的外侧部分。损伤产生的神经元表达纹状体中等棘状神经元（DARPP-32）和中间神经元（小白蛋白或神经肽Y）的表型标志物。神经发生的程度与纹状体损伤的大小相关。我们的数据首次表明，纹状体的兴奋性毒性损伤可触发具有投射神经元和中间神经元表型的新纹状体神经元的形成。
