Celsr3/Dlx小鼠皮质脊髓联系剥夺导致运动功能和脊髓运动神经元的变化  

Spinal motoneuron maturation and motor function changes in Celsr3 /Dlx mice with absent cortico-spinal connections

作　　者：林飚[1] 韩齐[1] 周立兵[1] 

机构地区：[1]暨南大学粤港澳中枢神经再生研究院,广州510632

出　　处：《神经解剖学杂志》2014年第3期261-266,共6页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(81171152);广东省高等学校高层次人才计划(50524005)

摘　　要：目的:研究去皮质联系后小鼠运动相关神经结构和运动功能的变化,以明确皮质输入信息对脊髓和神经肌接头成熟的影响。方法:应用皮质与皮质下联系在胚胎发育早期完全缺失的Celsr3/Dlx条件性基因敲除小鼠模型,通过旷场试验检测小鼠的自发运动;用乙酰胆碱酯酶(ChAT)免疫组织化学染色方法分析脊髓胆碱能运动神经元的数目变化;结合高尔基(Golgi)染色和神经元三维重建比较运动神经元树突分支数目和长度差异;最后采用免疫荧光双重标记(NF200和α-BT)和肌电图检测神经肌肉接头的形态和功能。结果:旷场试验表明与正常小鼠相比,Celsr3/Dlx小鼠过度活跃;这些小鼠脊髓运动神经元的总数目减少15%(P<0.01),其树突总长度也明显减少(P<0.01);此外形成神经肌肉接头运动神经元轴突末梢的分支数目及肌电图记录的峰值分别减少53%和47%(P<0.01)。结论:皮质的信息输入的缺失会导致脊髓运动神经元减少和神经肌肉接头的结构异常,而这些形态学的改变会进一步导致神经兴奋和传导的异常。Objective： To study changes of spinal motoneurons and motor function in mice with absent cortico-spinal connections and to clarify how much the maturation of the spinal cord and neuromuscular junctions （NMJs） depends on cortical inputs. Methods： Using Celsr3/Dlx mice, in which eortieo-subeortieal connections were genetically ablated during early development, we carried out open-field tests to measure the spontaneous locomotion, analyzed the number change of cholinergic motoneurons by immunostaining of choline acetyltransferase （ CHAT）, compared the dendritic length and branches of motoneurons by Golgi staining combined with three dimensional reconstruction, examined postsynaptic AchRs of NMJ clustering with ct-bungarotoxin （ct-BT） staining, and motor axon terminals with anti-neurofilament （NF200） staining, assessed NMJ function by recording the electromyograph （EMG）. Results： Open-field tests showed Celsr3/Dlx mice to be hyperactive. Compared with normal littermates, mutant animals reduced the number of spinal moto-neurons by 15% （ P 〈 0. 01 ） , with atrophic dendritic trees （ P 〈 0.01 ）. Futhermore, the motor axon terminals and the peak-to-peak amplitude of EMG recording in mutant mice were decreased by 53% and 47%, respectively （ P 〈 0.01 ）. Conclusion： The absence of cortical input results in the decrease of spinal motoneurons and abnormal NMJs, subsequently, the morphological abnormity cause an exception in nerved excitement and conduction.

关 键 词：皮质联系 运动神经元 Celsr3 小鼠 

分 类 号：R741[医药卫生—神经病学与精神病学]