Jure Ignacio, Pietranera Luciana, De Nicola Alejandro F, Labombarda Florencia
Laboratorio de Bioquímica Neuroendocrina, Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490, 1428, Buenos Aires, Argentina.
Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155 C1121 ABG, Buenos Aires, Argentina.
Neurochem Res. 2017 Aug;42(8):2178-2190. doi: 10.1007/s11064-017-2225-9. Epub 2017 Mar 13.
The incorporation of newborn neurons with increased synaptic remodeling and activity-dependent plasticity in the dentate gyrus enhances hippocampal-dependent learning performances. Astrocytes and microglial cells are components of the neurogenic niche and regulate neurogenesis under normal and neurophatological conditions leading to functional consequences for learning and memory. Although cognitive impairments were reported in patients after spinal cord injury (SCI), only few studies have considered remote changes in brain structures which are not related with sensory and motor cortex. Thus, we examined neurogenesis and glial reactivity by stereological assessment in dentate gyrus sub-regions after three different intensities of thoracic spinal cord compression in rats. Sixty days after injury we observed a decrease in the Basso-Bresnahan-Beattie locomotor scale scores, rotarod performance and volume of spare tissue that correlated with the severity of the compression. Regarding the hippocampus, we observed that neurogenesis and hilar neurons were reduced after severe SCI, while only neurogenesis decreased in the moderately injured group. In addition, severe SCI induced reactive microglia and astrogliosis in all dentate gyrus sub-regions. Furthermore, the density of reactive microglia increased in the hilus whereas astrogliosis developed in the molecular layer after moderate SCI. No changes were observed in the mildly injured rats. These results suggest glial response and neurogenesis are associated with injury intensity. Interestingly, hippocampal neurogenesis is more sensitive to SCI than astrocytes or microglia reaction, as moderate injury impairs the generation of new neurons without changing glial response in the subgranular zone.
新生神经元的整合以及齿状回中突触重塑和活动依赖性可塑性的增加，增强了海马体依赖性学习表现。星形胶质细胞和小胶质细胞是神经发生微环境的组成部分，在正常和神经病理条件下调节神经发生，从而对学习和记忆产生功能影响。尽管脊髓损伤（SCI）患者报告有认知障碍，但只有少数研究考虑了与感觉和运动皮层无关的脑结构的远程变化。因此，我们通过立体学评估，研究了大鼠在三种不同强度的胸段脊髓压迫后齿状回亚区域的神经发生和胶质细胞反应性。损伤60天后，我们观察到巴索-布雷斯纳汉-比蒂运动量表评分、转棒试验表现和备用组织体积下降，且这些下降与压迫的严重程度相关。关于海马体，我们观察到严重脊髓损伤后神经发生和门区神经元减少，而中度损伤组只有神经发生减少。此外，严重脊髓损伤在所有齿状回亚区域诱导了反应性小胶质细胞和星形胶质细胞增生。此外，中度脊髓损伤后门区反应性小胶质细胞密度增加，而分子层出现星形胶质细胞增生。轻度损伤的大鼠未观察到变化。这些结果表明，胶质细胞反应和神经发生与损伤强度有关。有趣的是，海马体神经发生比星形胶质细胞或小胶质细胞反应对脊髓损伤更敏感，因为中度损伤会损害新神经元的生成，而不会改变颗粒下区的胶质细胞反应。
