Toll-like receptor 4 differentially regulates adult hippocampal neurogenesis in an age- and sex-dependent manner.
Toll-like receptor 4 differentially regulates adult hippocampal neurogenesis in an age- and sex-dependent manner.
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DOI：
10.1002/hipo.23209
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发表时间：
2020-09
期刊：
影响因子：
3.5
通讯作者：
Kohman RA
中科院分区：
文献类型：
--
作者：
Connolly MG;Yost OL;Potter OV;Giedraitis ME;Kohman RA
Toll样受体4（TLR 4）主要负责在病原体识别后启动免疫应答。然而，TLR 4也在神经祖细胞上表达，并且已经报道调节海马神经发生，因为年轻的雄性TLR 4敲除小鼠显示细胞增殖和双皮质素阳性细胞增加。目前尚不清楚这些影响是否发生在两性身上，并在正常衰老过程中持续存在。本研究评估了TLR 4缺乏是否会改变年轻（3-4个月）和老年（18-20个月），雄性和雌性，TLR 4缺乏（TLR 4 −/−; B6. B10 ScN-Tlr 4lps-del/JthJ）和野生型（WT）小鼠的成年海马神经发生。此外，背侧和腹侧海马分区内的神经发生进行了评估，以确定TLR 4是否具有跨海马的差异效应。施用溴脱氧尿苷（BrdU）以定量新细胞存活以及细胞分化。检测Ki-67以评价细胞增殖。结果表明，年轻的TLR 4 −/−雌性在背侧和腹侧海马中的增殖和神经元分化率高于WT雌性。年轻的TLR 4 −/−雄性主要在腹侧海马中表现出升高的增殖和神经元分化。虽然与年轻的WT小鼠相比，年轻的TLR 4 −/−小鼠显示出增强的神经发生，但这种增加在老年TLR 4 −/−小鼠中并不明显。与年轻的WT和TLR 4 −/−小鼠相比，年老的WT和TLR 4 −/−小鼠的增殖、新细胞存活和神经元分化都有所减少。这些数据共同表明，TLR 4调节年轻成年人海马神经发生，但这些影响是区域特异性的男性和女性在整个海马神经发生显示更广泛的变化。
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.
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影响因子：
9.3
作者：
Littlefield AM;Setti SE;Priester C;Kohman RA
通讯作者：
Kohman RA
影响因子：
16.2
作者：
Fanselow, Michael S.;Dong, Hong-Wei
通讯作者：
Dong, Hong-Wei
影响因子：
9
作者：
Grasselli C;Ferrari D;Zalfa C;Soncini M;Mazzoccoli G;Facchini FA;Marongiu L;Granucci F;Copetti M;Vescovi AL;Peri F;De Filippis L
通讯作者：
De Filippis L
影响因子：
9.3
作者：
Cribbs DH;Berchtold NC;Perreau V;Coleman PD;Rogers J;Tenner AJ;Cotman CW
通讯作者：
Cotman CW
影响因子：
3.5
作者：
Duarte-Guterman, Paula;Yagi, Shunya;Galea, Liisa A. M.
通讯作者：
Galea, Liisa A. M.