Toll‐like receptor 4 (TLR4) is primarily responsible for initiating an immune response following pathogen recognition. However, TLR4 is also expressed on neural progenitor cells and has been reported to regulate hippocampal neurogenesis as young male TLR4 knockout mice show increases in cell proliferation and doublecortin positive cells. Whether these effects occur in both sexes and are sustained with normal aging is currently unknown. The present study evaluated whether TLR4 deficiency alters adult hippocampal neurogenesis in young (3–4 months) and aged (18–20 months), male and female, TLR4 deficient (TLR4−/−; B6.B10ScN‐Tlr4lps‐del/JthJ) and wild type (WT) mice. Additionally, neurogenesis within the dorsal and the ventral hippocampal subdivisions was evaluated to determine if TLR4 has differential effects across the hippocampus. Bromodeoxyuridine (BrdU) was administered to quantify new cell survival as well as cell differentiation. Ki‐67 was measured to evaluate cell proliferation. Results show that young TLR4−/− females had higher rates of proliferation and neuronal differentiation in both the dorsal and ventral hippocampus relative to WT females. Young TLR4−/− males show elevated proliferation and neuronal differentiation mainly in the ventral hippocampus. While young TLR4−/− mice show enhanced neurogenesis compared to young WT mice, the increase was not apparent in the aged TLR4−/− mice. Both aged WT and TLR4−/− mice showed a decrease in proliferation, new cell survival, and neuronal differentiation compared to young WT and TLR4−/− mice. The data collectively indicate that TLR4 regulates hippocampal neurogenesis in young adults, but that these effects are region‐specific in males and that females show broader changes in neurogenesis throughout the hippocampus.

中文翻译：

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Toll 样受体 4 以年龄和性别依赖性方式差异调节成年海马神经发生。

Toll 样受体 4 (TLR4) 主要负责在病原体识别后启动免疫反应。然而，TLR4 也在神经祖细胞上表达，据报道，随着年轻雄性 TLR4 敲除小鼠的细胞增殖和双皮质素阳性细胞的增加，TLR4 可调节海马神经发生。这些影响是否在两性中都发生并随着正常衰老而持续目前尚不清楚。本研究评估了 TLR4 缺乏是否会改变年轻人（3-4 个月）和老年人（18-20 个月）、男性和女性、TLR4 缺陷（TLR4-/-；B6.B10ScN-Tlr4lps-del/JthJ）的成年海马神经发生和野生型 (WT) 小鼠。此外，还评估了背侧和腹侧海马细分内的神经发生，以确定 TLR4 是否对整个海马具有不同的影响。给予溴脱氧尿苷 (BrdU) 以量化新细胞存活以及细胞分化。测量 Ki-67 以评估细胞增殖。结果表明，与 WT 雌性相比，年轻的 TLR4-/- 雌性在背侧和腹侧海马体中具有更高的增殖率和神经元分化率。年轻的 TLR4-/- 雄性主要在腹侧海马中表现出增殖和神经元分化升高。虽然与年轻的 WT 小鼠相比，年轻的 TLR4-/- 小鼠显示出增强的神经发生，但在老年 TLR4-/- 小鼠中这种增加并不明显。与年轻的 WT 和 TLR4-/- 小鼠相比，年老的 WT 和 TLR4-/- 小鼠的增殖、新细胞存活率和神经元分化均有所下降。数据共同表明 TLR4 调节年轻人的海马神经发生，