Department of Anatomy and Neurobiology, Kyushu University, Fukuoka, Japan.
J Comp Neurol. 2011 Feb 15;519(3):451-66. doi: 10.1002/cne.22527.
In the rodent brain, diverse functions are topographically distributed within the hippocampus. For instance, the dorsal (septal) hippocampus is involved in spatial memory, whereas the ventral (temporal) hippocampus is related to emotion and anxiety. Accumulating evidence shows that age-dependent decline in hippocampal neurogenesis is associated with impairments of these functions. However, little is known about whether the decline in dentate granule cell production during aging follows a topographic pattern. Here we quantitatively estimated specific populations of adult-born cells in young adult and middle-aged mice by using endogenous markers and determined whether age-dependent reductions in adult neurogenesis exhibited topographic differences. The numerical densities (NDs) of putative primary progenitors, intermediate neuronal progenitors, and neuronal lineages were higher in the dorsal dentate gyrus (DG) than in the ventral DG both in young adult and in middle-aged mice, but the ratios of the NDs in the dorsal DG to the NDs in the ventral DG noticeably increased with age. The age-related reductions in the numbers of these populations were larger in the ventral DG than in the dorsal DG. By contrast, the NDs of glial lineages were higher in the ventral DG than in the dorsal DG during life, and the numbers of glial lineages showed no significant age-related changes. Our findings suggest that neurogenesis, but not gliogenesis, wanes faster in the ventral hippocampus than in the dorsal hippocampus during aging. Such age-related topographic changes in hippocampal neurogenesis might be implicated in memory and affective impairments in older people.
在啮齿动物大脑中，不同的功能在海马体中呈现出拓扑分布。例如，背（隔区）海马体参与空间记忆，而腹（颞叶）海马体与情绪和焦虑有关。越来越多的证据表明，海马体神经发生的年龄依赖性下降与这些功能的损伤有关。然而，人们对衰老过程中齿状回颗粒细胞产生的下降是否遵循地形模式知之甚少。在这里，我们通过使用内源性标记物定量估计了年轻成年和中年小鼠中特定的成年新生细胞群体，并确定了成年神经发生的年龄依赖性减少是否表现出地形差异。在年轻成年和中年小鼠中，背侧齿状回（DG）中的假定初级祖细胞、中间神经元祖细胞和神经元谱系的数量密度（ND）均高于腹侧 DG，但背侧 DG 与腹侧 DG 的 ND 比值随着年龄的增长明显增加。与背侧 DG 相比，这些群体数量的年龄相关性减少在腹侧 DG 中更大。相比之下，在整个生命过程中，腹侧 DG 中的神经胶质谱系的 ND 高于背侧 DG，而神经胶质谱系的数量没有明显的年龄相关性变化。我们的研究结果表明，在衰老过程中，神经发生而不是神经胶质发生在腹侧海马体中比在背侧海马体中下降得更快。海马体神经发生的这种与年龄相关的地形变化可能与老年人的记忆和情感障碍有关。
