Sexual dimorphism is evident in brain structure, size, and function throughout multiple species. Here, we tested whether cerebrospinal fluid entry into the glymphatic system, a network of perivascular fluid transport that clears metabolic waste from the brain, was altered between male and female mice. We analyze glymphatic influx in 244 young reproductive age (2–4 months) C57BL/6 mice. We found no male/female differences in total influx under anesthesia, or across the anterior/posterior axis of the brain. Circadian-dependent changes in glymphatic influx under ketamine/xylazine anesthesia were not altered by sex. This was not true for diurnal rhythms under pentobarbital and avertin, but both still showed daily oscillations independent of biological sex. Finally, although glymphatic influx decreases with age there was no sex difference in total influx or subregion-dependent tracer distribution in 17 middle aged (9–10 months) and 36 old (22–24 months) mice. Overall, in healthy adult C57BL/6 mice we could not detect male/female differences in glymphatic influx. This finding contrasts the gender differences in common neurodegenerative diseases. We propose that additional sex-dependent co-morbidities, such as chronic stress, protein misfolding, traumatic brain injury or other pathological mechanisms may explain the increased risk for developing proteinopathies rather than pre-existing suppression of glymphatic influx.

性别二态性在多个物种的大脑结构、大小和功能中都很明显。在这里，我们测试了脑脊液进入淋巴系统（一种清除大脑代谢废物的血管周围液体转运网络）是否在雄性和雌性小鼠之间发生了改变。我们分析了 244 只年轻育龄（2-4 个月）C57BL/6 小鼠的淋巴流入。我们发现在麻醉下或跨大脑前/后轴的总流入量没有男性/女性差异。氯胺酮/甲苯噻嗪麻醉下淋巴内流的昼夜依赖性变化并未因性别而改变。在戊巴比妥和阿佛丁下的昼夜节律并非如此，但两者仍显示出与生物性别无关的每日振荡。最后，尽管 glymphatic 流入量随着年龄的增长而减少，但在 17 只中年（9-10 个月）和 36 只老年（22-24 个月）小鼠中，总流入量或亚区域依赖性示踪剂分布没有性别差异。总体而言，在健康的成年 C57BL/6 小鼠中，我们无法检测到淋巴流入的雄性/雌性差异。这一发现对比了常见神经退行性疾病的性别差异。我们提出，其他与性别相关的合并症，例如慢性压力、蛋白质错误折叠、创伤性脑损伤或其他病理机制，可以解释发生蛋白质病的风险增加，而不是先前存在的淋巴流入抑制。在健康的成年 C57BL/6 小鼠中，我们无法检测到雄性/雌性淋巴流入的差异。这一发现对比了常见神经退行性疾病的性别差异。我们提出，其他与性别相关的合并症，例如慢性压力、蛋白质错误折叠、创伤性脑损伤或其他病理机制，可以解释发生蛋白质病的风险增加，而不是先前存在的淋巴流入抑制。在健康的成年 C57BL/6 小鼠中，我们无法检测到雄性/雌性淋巴流入的差异。这一发现对比了常见神经退行性疾病的性别差异。我们提出，其他与性别相关的合并症，例如慢性压力、蛋白质错误折叠、创伤性脑损伤或其他病理机制，可以解释发生蛋白质病的风险增加，而不是先前存在的淋巴流入抑制。