Prenatal infection and adolescent social adversity affect microglia, synaptic density, and behavior in male rats

IF 4.3 2区 医学 Q1 NEUROSCIENCES Neurobiology of Stress Pub Date : 2023-10-19 DOI:10.1016/j.ynstr.2023.100580
Cyprien G.J. Guerrin , Kavya Prasad , Daniel A. Vazquez-Matias , Jing Zheng , Maria Franquesa-Mullerat , Lara Barazzuol , Janine Doorduin , Erik F.J. de Vries
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Abstract

Maternal infection during pregnancy and childhood social trauma have been associated with neurodevelopmental and affective disorders, such as schizophrenia, autism spectrum disorders, bipolar disorder and depression. These disorders are characterized by changes in microglial cells, which play a notable role in synaptic pruning, and synaptic deficits. Here, we investigated the effect of prenatal infection and social adversity during adolescence – either alone or in combination – on behavior, microglia, and synaptic density. Male offspring of pregnant rats injected with poly I:C, mimicking prenatal infection, were exposed to repeated social defeat during adolescence. We found that maternal infection during pregnancy prevented the reduction in social behavior and increase in anxiety induced by social adversity during adolescence. Furthermore, maternal infection and social adversity, alone or in combination, induced hyperlocomotion in adulthood. Longitudinal in vivo imaging with [11C]PBR28 positron emission tomography revealed that prenatal infection alone and social adversity during adolescence alone induced a transient increase in translocator protein TSPO density, an indicator of glial reactivity, whereas their combination induced a long-lasting increase that remained until adulthood. Furthermore, only the combination of prenatal infection and social adversity during adolescence induced an increase in microglial cell density in the frontal cortex. Prenatal infection increased proinflammatory cytokine IL-1β protein levels in hippocampus and social adversity reduced anti-inflammatory cytokine IL-10 protein levels in hippocampus during adulthood. This reduction in IL-10 was prevented if rats were previously exposed to prenatal infection. Adult offspring exposed to prenatal infection or adolescent social adversity had a higher synaptic density in the frontal cortex, but not hippocampus, as evaluated by synaptophysin density. Interestingly, such an increase in synaptic density was not observed in rats exposed to the combination of prenatal infection and social adversity, perhaps due to the long-lasting increase in microglial density, which may lead to an increase in microglial synaptic pruning. These findings suggest that changes in microglia activity and cytokine release induced by prenatal infection and social adversity during adolescence may be related to a reduced synaptic pruning, resulting in a higher synaptic density and behavioral changes in adulthood.

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产前感染和青少年社会逆境对雄性大鼠小胶质细胞、突触密度和行为的影响
妊娠期和儿童期的母亲感染社会创伤与神经发育和情感障碍有关,如精神分裂症、自闭症谱系障碍、双相情感障碍和抑郁症。这些疾病的特征是小胶质细胞的变化,小胶质细胞在突触修剪和突触缺陷中发挥着显著作用。在这里,我们研究了产前感染和青春期社会逆境(单独或联合)对行为、小胶质细胞和突触密度的影响。注射poly I:C的怀孕大鼠的雄性后代,模仿产前感染,在青春期暴露于反复的社会失败中。我们发现,怀孕期间的母亲感染阻止了青春期社会逆境引起的社交行为的减少和焦虑的增加。此外,母亲感染和社会逆境,无论是单独还是组合,都会导致成年后的过度运动。[11C]PBR28正电子发射断层扫描的纵向体内成像显示,单独的产前感染和青春期的社会逆境诱导了转运蛋白TSPO密度的短暂增加,TSPO密度是神经胶质反应性的指标,而它们的组合诱导了持续到成年的长期增加。此外,只有产前感染和青春期社会逆境的结合才导致额叶皮层小胶质细胞密度增加。在成年期,产前感染增加了海马中的促炎细胞因子IL-1β蛋白水平,而社会逆境降低了海马中抗炎细胞因子IL-10蛋白水平。如果大鼠先前暴露于产前感染,则可以防止IL-10的这种减少。根据突触素密度评估,暴露于产前感染或青少年社会逆境的成年后代额叶皮层的突触密度较高,但海马体的突触密度不高。有趣的是,在暴露于产前感染和社会逆境的大鼠中没有观察到突触密度的这种增加,可能是由于小胶质细胞密度的长期增加,这可能导致小胶质细胞突触修剪的增加。这些发现表明,产前感染和青春期社会逆境诱导的小胶质细胞活性和细胞因子释放的变化可能与突触修剪减少有关,从而导致成年后突触密度和行为变化增加。
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来源期刊
Neurobiology of Stress
Neurobiology of Stress Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
9.40
自引率
4.00%
发文量
74
审稿时长
48 days
期刊介绍: Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal. Basic, translational and clinical research on the following topics as they relate to stress will be covered: Molecular substrates and cell signaling, Genetics and epigenetics, Stress circuitry, Structural and physiological plasticity, Developmental Aspects, Laboratory models of stress, Neuroinflammation and pathology, Memory and Cognition, Motivational Processes, Fear and Anxiety, Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse), Neuropsychopharmacology.
期刊最新文献
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