Poulen Gaëtan, Douich Nacéra, Gazard Chloé M, Mestre-Francés Nadine, Cardoso Maïda, Bauchet Luc, Vachiery-Lahaye Florence, Lonjon Nicolas, Gerber Yannick N, Perrin Florence E
MMDN, Univ. Montpellier, EPHE, INSERM, Montpellier, France.
Department of Neurosurgery, CHU, Montpellier, France.
Cell Death Discov. 2025 Apr 2;11(1):129. doi: 10.1038/s41420-025-02425-9.
In a healthy central nervous system, glial cells are influenced by genetic, epigenetic, age, and sex factors. Aging typically causes astrocytes and microglia to undergo changes that reduce their neuroprotective functions and increase harmful activities. Additionally, sex-related differences in glial and myelin functions may impact neurological disorders. Despite this, few studies have investigated glial cells in primates, with most focusing on the brain. This study aims to explore whether glial cells and myelin exhibit age- and sex-related differences in the spinal cord of nonhuman primates and humans. We used immunohistochemistry and myelin staining to analyze healthy spinal cord samples from midlife and aged individuals of both sexes, focusing on Microcebus murinus (a small nonhuman primate) and humans. Primate spinal cords show distinct variations in glial markers and myelin characteristics related to sex and age, with differences varying between species. Notably, GFAP expression is sex-dependent in both primate species. We also observed greater differences in the expression of microglial markers than other glial markers. Overall, we found the opposite pattern for the g-ratio and oligodendrocytic marker between species. These findings suggest that glial cells may play a critical role in age- and sex-related differences in the prevalence and progression of spinal cord diseases.
在健康的中枢神经系统中，神经胶质细胞受到遗传、表观遗传、年龄和性别因素的影响。衰老通常会导致星形胶质细胞和小胶质细胞发生变化，从而降低它们的神经保护功能并增加有害活动。此外，神经胶质细胞和髓鞘功能的性别相关差异可能会影响神经疾病。尽管如此，很少有研究调查灵长类动物的神经胶质细胞，大多数研究集中在大脑。本研究旨在探讨神经胶质细胞和髓鞘在非人类灵长类动物和人类的脊髓中是否存在与年龄和性别相关的差异。我们使用免疫组织化学和髓鞘染色来分析中年和老年两性个体的健康脊髓样本，重点研究小倭狐猴（一种小型非人类灵长类动物）和人类。灵长类动物的脊髓在神经胶质标记物和与性别及年龄相关的髓鞘特征方面表现出明显差异，不同物种之间的差异各不相同。值得注意的是，在这两种灵长类动物中，胶质纤维酸性蛋白（GFAP）的表达都依赖于性别。我们还观察到，与其他神经胶质标记物相比，小胶质细胞标记物的表达差异更大。总体而言，我们发现不同物种之间在g比值和少突胶质细胞标记物方面呈现出相反的模式。这些发现表明，神经胶质细胞可能在脊髓疾病的患病率和进展的年龄及性别相关差异中起关键作用。
