Differences in microglia morphological profiles reflect divergent emotional temperaments: insights from a selective breeding model.
Differences in microglia morphological profiles reflect divergent emotional temperaments: insights from a selective breeding model.
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DOI：
10.1038/s41398-022-01821-4
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发表时间：
2022-03-15
影响因子：
6.8
通讯作者：
Akil H
中科院分区：
文献类型：
--
作者：
Maras PM;Hebda-Bauer EK;Hagenauer MH;Hilde KL;Blandino P Jr;Watson SJ Jr;Akil H
小胶质细胞在健康的大脑发育和功能以及一系列脑部疾病的神经病理学中发挥着关键作用。尽管有证据表明小胶质细胞在情感调节和情绪障碍中的作用，但关于小胶质细胞状态的变化如何与情绪的个体差异有关却知之甚少。使用选择性育种模型，我们已经产生了独特的气质表型，反映了广泛的情感特征的大鼠品系：繁殖低反应大鼠（BLR）是新奇厌恶和模型的被动应对方式，而繁殖高反应大鼠（BHR）是高度探索和模型的积极应对方式。为了确定小胶质细胞在这些表型中的功能作用，我们给予米诺环素，一种具有强效小胶质细胞抑制特性的抗生素，并观察到强迫游泳，蔗糖偏好和bLR中的社会互动行为的变化。使用详细的解剖学分析，我们比较了海马小胶质细胞的bHR和bLR的配置文件，并发现，虽然线有类似数量的小胶质细胞，选择性繁殖与这些细胞的形态特征的转变。具体而言，从bLR的小胶质细胞的特征在于一个超分枝形态，更长的过程和更复杂的分支模式比小胶质细胞从bHR。这种形态被认为反映了小胶质细胞活化的早期阶段，并表明即使动物没有受到明显的挑战，bLR小胶质细胞也处于反应状态。总之，我们的研究结果提供了新的证据，将先天气质的变化与小胶质细胞基线状态的差异联系起来，并暗示了小胶质细胞在塑造持久的情感特征中的作用。
Microglia play critical roles in healthy brain development and function, as well as the neuropathology underlying a range of brain diseases. Despite evidence for a role of microglia in affective regulation and mood disorders, little is known regarding how variation in microglia status relates to individual differences in emotionality. Using a selective breeding model, we have generated rat lines with unique temperamental phenotypes that reflect broad emotional traits: bred low responder rats (bLRs) are novelty-averse and model a passive coping style, whereas bred high responder rats (bHRs) are highly exploratory and model an active coping style. To identify a functional role of microglia in these phenotypes, we administered minocycline, an antibiotic with potent microglia inhibiting properties and observed shifts in forced swim, sucrose preference, and social interaction behaviors in bLRs. Using detailed anatomical analyses, we compared hippocampal microglia profiles of bHRs and bLRs and found that although the lines had similar numbers of microglia, selective breeding was associated with a shift in the morphological features of these cells. Specifically, microglia from bLRs were characterized by a hyper-ramified morphology, with longer processes and more complicated branching patterns than microglia from bHRs. This morphology is thought to reflect an early stage of microglia activation and suggests that bLR microglia are in a reactive state even when animals are not overtly challenged. Taken together, our results provide novel evidence linking variation in inborn temperament with differences in the baseline status of microglia and implicate a role for microglia in shaping enduring emotional characteristics.
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影响因子：
3.5
作者：
Clinton, Sarah M.;Bedrosian, Tracy A.;Abraham, Antony D.;Watson, Stanley J.;Akil, Huda
通讯作者：
Akil, Huda
影响因子：
6.2
作者：
Duarte, Joana Mendes;Gaspar, Rita;Gomes, Catarina A.
通讯作者：
Gomes, Catarina A.
影响因子：
10.6
作者：
Birt IA;Hagenauer MH;Clinton SM;Aydin C;Blandino P Jr;Stead JDH;Hilde KL;Meng F;Thompson RC;Khalil H;Stefanov A;Maras P;Zhou Z;Hebda-Bauer EK;Goldman D;Watson SJ Jr;Akil H
通讯作者：
Akil H
影响因子：
7.4
作者：
Gladstone, GL;Parker, GB;Malhi, GS
通讯作者：
Malhi, GS
影响因子：
3.3
作者：
Glover ME;Cohen JL;Singer JR;Sabbagh MN;Rainville JR;Hyland MT;Morrow CD;Weaver CT;Hodes GE;Kerman IA;Clinton SM
通讯作者：
Clinton SM