The Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.
Department of Biological Chemistry, Life Science Institute, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel.
J Neuroimmune Pharmacol. 2019 Jun;14(2):251-262. doi: 10.1007/s11481-018-9817-2. Epub 2018 Oct 20.
Effect of age and ladostigil treatment (1 mg/kg/day), given for 6 months to 16 month old rats, was investigated on microglial morphology in brain regions associated with control of spatial learning. This was assessed in the Morris water maze (MWM). Microglial morphology was assessed with diaminobenzidine and fluorescent staining with Iba1 and CD11b in these brain regions. Aging did not change the number of microglia in the parietal cortex (PC) or hippocampal CA1 region (CA1-HC), but decreased microglial process tips in the CA1-HC, increased the area fraction stained by CD11b and number of bulbs on processes in PC and CA1-HC and thickness of microglial processes in corpus callosum (CC) and fornix (Fx). Performance in MWM (distance swam to escape platform) was negatively correlated with number of bulbs in PC and thickness of process in CC, and positively correlated with number of process tips in CA1-HC. Aging increased expression of MHC class II genes and others associated with motility and membrane adhesion in the PC and hippocampus, but Adora2a (Adenosine A2a receptor), only in hippocampus. Age-related increase in the number of bulbs and expression of inflammatory genes was prevented by ladostigil in PC. In the CA1-HC, ladostigil increased the number of process tips and prevented the increase in expression of Adora2a and genes regulating ion channels. Ladostigil also decreased thickening of the processes in CC and Fx. The data show brain region-specific relations induced by age in spatial learning, microglial morphology and associated genes and their response to ladostigil treatment. Graphical Abstract.
年龄和 ladostigil 治疗（1mg/kg/天）对 6 个月至 16 个月大的大鼠大脑中与空间学习控制相关区域小胶质细胞形态的影响进行了研究。这是在 Morris 水迷宫（MWM）中进行评估的。用二氨基联苯胺和 Iba1 和 CD11b 的荧光染色评估这些大脑区域中小胶质细胞的形态。衰老不会改变顶叶皮层（PC）或海马 CA1 区（CA1-HC）中小胶质细胞的数量，但会减少 CA1-HC 中小胶质细胞突起的尖端，增加 PC 和 CA1-HC 中 CD11b 染色的面积分数和突起上的小球数量，以及胼胝体（CC）和穹窿（Fx）中小胶质细胞突起的厚度。MWM 中的表现（游到逃生平台的距离）与 PC 中的小球数量和 CC 中过程的厚度呈负相关，与 CA1-HC 中的过程尖端数量呈正相关。衰老增加了 PC 和海马中与运动性和膜粘附相关的 MHC 类 II 基因和其他基因的表达，但 Adora2a（腺苷 A2a 受体）仅在海马中增加。 ladostigil 可预防 PC 中年龄相关性小球数量增加和炎症基因表达增加。在 CA1-HC 中，ladostigil 增加了突起尖端的数量，并防止了 Adora2a 和调节离子通道的基因表达增加。 ladostigil 还减少了 CC 和 Fx 中过程的增厚。这些数据显示了与年龄相关的空间学习、小胶质细胞形态及其相关基因的大脑区域特异性关系，以及它们对 ladostigil 治疗的反应。图表摘要。
