Department of Anatomy and Neuroscience, University College Cork, Ireland.
Department of Anatomy and Neuroscience, University College Cork, Ireland; APC Microbiome Ireland, University College Cork, Ireland.
Brain Behav Immun. 2022 Jan;99:327-338. doi: 10.1016/j.bbi.2021.10.016. Epub 2021 Oct 31.
Stress during critical periods of neurodevelopment is associated with an increased risk of developing stress-related psychiatric disorders, which are more common in women than men. Hippocampal neurogenesis (the birth of new neurons) is vulnerable to maternal separation (MS) and inflammatory stressors, and emerging evidence suggests that hippocampal neurogenesis is more sensitive to stress in the ventral hippocampus (vHi) than in the dorsal hippocampus (dHi). Although research into the effects of MS stress on hippocampal neurogenesis is well documented in male rodents, the effect in females remains underexplored. Similarly, reports on the impact of inflammatory stressors on hippocampal neurogenesis in females are limited, especially when female bias in the prevalence of stress-related psychiatric disorders begins to emerge. Thus, in this study we investigated the effects of MS followed by an inflammatory stressor (lipopolysaccharide, LPS) in early adolescence on peripheral and hippocampal inflammatory responses and hippocampal neurogenesis in juvenile female rats. We show that MS enhanced an LPS-induced increase in the pro-inflammatory cytokine IL-1β in the vHi but not in the dHi. However, microglial activation was similar following LPS alone or MS alone in both hippocampal regions, while MS prior to LPS reduced microglial activation in both dHi and vHi. The production of new neurons was unaffected by MS and LPS. MS and LPS independently reduced the dendritic complexity of new neurons, and MS exacerbated LPS-induced reductions in the complexity of distal dendrites of new neurons in the vHi but not dHi. These data highlight that MS differentially primes the physiological response to LPS in the juvenile female rat hippocampus.
神经发育关键期的应激与应激相关精神障碍的发病风险增加有关，而应激相关精神障碍在女性中比男性更为常见。海马神经发生（新神经元的产生）易受母婴分离（MS）和炎症应激源的影响，新出现的证据表明，海马神经发生对腹侧海马（vHi）的应激比背侧海马（dHi）更为敏感。虽然 MS 应激对雄性啮齿动物海马神经发生的影响已有充分的研究，但在雌性动物中的影响仍未得到充分探索。同样，关于炎症应激源对雌性海马神经发生影响的报告也很有限，尤其是当应激相关精神障碍的患病率中女性偏见开始显现时。因此，在这项研究中，我们研究了青春期早期 MS 后再加上炎症应激源（脂多糖，LPS）对幼年雌性大鼠外周和海马炎症反应以及海马神经发生的影响。我们发现，MS 增强了 LPS 诱导的 vHi 中促炎细胞因子 IL-1β的增加，但在 dHi 中则没有。然而，单独给予 LPS 或 MS 后，两个海马区域的小胶质细胞激活相似，而 LPS 之前的 MS 减少了两个 dHi 和 vHi 中的小胶质细胞激活。新神经元的产生不受 MS 和 LPS 的影响。MS 和 LPS 独立地降低了新神经元的树突复杂性，而 MS 加剧了 LPS 诱导的 vHi 中新神经元远端树突复杂性的降低，但在 dHi 中则没有。这些数据突出表明，MS 以不同的方式使幼年雌性大鼠海马对 LPS 的生理反应致敏。
