oligodendrocytes migrate from the corpus callosum into the overlying cortex. The incidence of cilia did not change markedly across age groups, and did not vary consistently with the number of processes per cell, which was used as an indication of the maturation stage of OPCs and young OLs. The mean percent of Olig1 immunopositive (Olig1+) cells having cilia across ages was 33.1% + 16.5%, with all ages combined. In O4+ cells of these mice, 56.7 + 3.6% had primary cilia. If it is the case that adult OLs do not have cilia, the point in the lineage when primary cilia are lost is still unknown. Adult mice that had been injected with cyclopamine to block cilia-dependent Shh signaling were examined to determine whether the rate of generating new OPCs was influenced. In the CC of control mice, the numerical density of Olig1+/BrdU+ cells was 1.29 + 0.07/mm2 was reduced to 0.68 + 0.38/mm2 in the cyclopamine-injected group, and the numerical density of all BrdU+ cells (including both Olig1+ and Olig1- cells) of 4.55 + 1.50/mm2 in the control group was reduced to 3.14 + 1.27/mm2 in the cyclopamine-injected group. However, there were only 2 mice in each group and the differences were not statistically significant.

Each year, aging and age-related deficits in cognitive function affect larger population worldwide. Research on aging has focused on changes in gray matter and white matter with age. A quantitative analysis of magnetic resonance images from healthy subjects of 16-79 years showed a significant negative correlation between gray matter volume and age (Taki et al., 2004). In addition, age-related cognitive decline is reported to be associated with white matter changes such as myelin damage, a result of both the inability of microglia to clear out damaged myelin debris and oligodendrocyte to support remyelination. Eotaxin-1 (CCL11) belongs to a group of eosinophil-specific chemoattractant originally found in peripheral immune system mediating allergic inflammation, asthma and atopic dermatitis (Garcia-Zepeda et al., 1996; Spergel, Mizoguchi, Oettgen, Bhan, & Geha, 1999). Recently it has been reported to have endogenous sources in the CNS and to increase with age in cerebral spinal fluid (CSF) as well as periphery in blood plasma. While CCL11 has been identified to increase with age, injection of CCL11 inhibit neurogenesis in young mice, which is likely to be mediated by C-C chemokine receptor type 3 (CCR3). CCR3 is also the only receptor for CCL11 that is expressed by oligodendrocyte precursor cells (OPCs) and by activated microglia in mice, which means it may participate in the process of microglial phagocytosis and oligodendrocyte myelination. To investigate if CCR3 is an important factor in the normal aging brain and its potential role in these existing findings, immunohistochemistry, stereology and densitometry were performed in the anterior cingulate cortex and cingulum from brain tissue of 4 young adults and 6 aged rhesus monkeys that were behaviorally tested previously to 1) demonstrate any association between CCR3 expression level and age 2) characterize changes in CCR3 level in relation to cognitive impairment 3) identify cellular localization of CCR3. We found a significant increase in amount of CCR3 cingulate cortex with age, which suggests its pro-disease effect in other pathways such as the interaction between CNS and T cell immune system. Although for aged group increase in CCR3+ cell density in white matter appeared insignificant, we found that CCR3 was expressed exclusively in OPCs but was absent in mature oligodendrocytes. indicating its role in OPC proliferation, oligodendrocyte maturation and myelination.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22040号 / 医博第4525号 / 新制||医||1038(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 高橋 淳, 教授 伊佐 正, 教授 渡邉 大 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22336号 / 医博第4577号 / 新制||医||1041(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 高橋 淳, 教授 渡邉 大, 教授 伊佐 正 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM