Fréchette Mylène, Rennie Kerry, Pappas Bruce A
Institute of Neuroscience, Carleton University, Ottawa, Ontario, Canada K1S 5B6.
Brain Res. 2009 Feb 3;1252:172-82. doi: 10.1016/j.brainres.2008.11.082. Epub 2008 Dec 3.
Intraventricular injections of 192 IgG saporin in 7-day-old rat severely reduced hippocampal cholinergic innervation as reflected by both decreased acetylcholinesterase staining and immunoreactivity for the p75 neurotrophin receptor. It was determined if this altered the effects of environmental enrichment on spatial learning, hippocampal CA1 cell cytoarchitecture as reflected by the Golgi stain, and neurogenesis in the dentate gyrus as indicated by doublecortin immunoreactivity. At weaning, lesioned and control rats were either group housed in large, environmentally enriched cages or housed two per standard cage for 42 days. When subsequently assessed with a working-memory spatial navigation task, both lesioned and control rats showed enhanced learning as a result of enrichment. Quantitative analysis of Golgi stained sections indicated that enrichment did not affect CA1 dendritic branching, total dendritic length or dendritic spine density. However, the lesion reduced the number of apical branches, spine density on intermediate to distal apical dendrites, and the length of basal branches. It also reduced the number of doublecortin immunoreactive neurons in the dentate gyrus and appeared to prevent their increase due to environmental enrichment. It is concluded that developmental cholinergic lesioning does not attenuate neurobehavioral plasticity, at least as reflected by the behavioral consequences of enrichment. It does, however, attenuate neurogenesis in the dentate gyrus, like adult-inflicted cholinergic lesions. As previously found for cortical neurons, it also reduces CA1 pyramidal cell dendritic complexity and spine density in adulthood. The results have implications for the loss of synapses that occurs in both developmental and aging-related brain disorders involving cholinergic dysfunction.
在7日龄大鼠脑室内注射192 IgG皂草素可严重减少海马胆碱能神经支配，这可通过乙酰胆碱酯酶染色减少以及p75神经营养因子受体免疫反应性降低反映出来。研究确定这是否改变了环境丰富化对空间学习、高尔基染色所反映的海马CA1细胞细胞结构以及双皮质素免疫反应性所指示的齿状回神经发生的影响。在断奶时，损伤组和对照组大鼠要么群居在大型、环境丰富的笼子里，要么每两个置于标准笼子里饲养42天。随后用工作记忆空间导航任务进行评估时，损伤组和对照组大鼠由于环境丰富化学习能力均得到增强。对高尔基染色切片的定量分析表明，环境丰富化并未影响CA1树突分支、总树突长度或树突棘密度。然而，损伤减少了顶枝数量、中间至远端顶树突上的棘密度以及基枝长度。它还减少了齿状回中双皮质素免疫反应性神经元的数量，并且似乎阻止了由于环境丰富化导致的其数量增加。得出的结论是，发育性胆碱能损伤不会减弱神经行为可塑性，至少从环境丰富化的行为后果来看是这样。然而，它确实会减弱齿状回中的神经发生，就像成年期造成的胆碱能损伤一样。如先前在皮质神经元中所发现的，它还会在成年期降低CA1锥体细胞的树突复杂性和棘密度。这些结果对于在涉及胆碱能功能障碍的发育性和衰老相关脑疾病中发生的突触丧失具有启示意义。
