Maternal high-fat diet modifies myelin organization, microglial interactions, and results in social memory and sensorimotor gating deficits in adolescent mouse offspring.
Maternal high-fat diet modifies myelin organization, microglial interactions, and results in social memory and sensorimotor gating deficits in adolescent mouse offspring.
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DOI：
10.1016/j.bbih.2021.100281
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Tremblay MÈ
中科院分区：
文献类型：
--
作者：
Bordeleau M;Fernández de Cossío L;Lacabanne C;Savage JC;Vernoux N;Chakravarty M;Tremblay MÈ
产前暴露于母体高脂饮食（mHFD）是后代各种神经发育改变的风险因素。最近对小鼠的研究表明，mHFD导致暴露后代的神经炎症和髓鞘形成不足。小胶质细胞，即脑内巨噬细胞，在脑发育过程中起着至关重要的作用，特别是通过调节少突胶质细胞群和吞噬髓鞘。以前，我们报道mHFD改变小胶质细胞表型（即，形态学、与其微环境的相互作用、转录物）在雄性和雌性后代的海马体中的作用。在目前的研究中，我们进一步探讨mHFD是否可能诱导髓鞘形成的变化之间的胼胝体-前额叶皮层通路，并导致在青少年后代的行为结果的两种性别。为此，雌性小鼠在交配前、妊娠期间和直至其窝仔断奶时用对照饲料或HFD喂养4周。组织学和超微结构分析显示，与雌性后代相比，暴露于mHFD的雄性大鼠胼胝体中髓鞘密度增加，与胞质髓鞘通道面积减少相关。髓鞘形成相关基因的转录物，包括小胶质细胞释放的生长因子Igf 1，也较低，特别是在青春期雄性小鼠后代的海马体（前额叶皮质没有变化）中。髓鞘的这些变化与少突胶质细胞的密度、分布或成熟改变无关，相反，我们发现暴露于mHFD的后代的胼胝体内的小胶质细胞显示成熟溶酶体数量减少和突触接触增加，表明小胶质细胞在修饰的髓鞘形成中的作用。在行为水平，男性和女性mHFD暴露的青少年后代的社会记忆和感觉运动门控缺陷的损失。这些结果共同强调了研究少突胶质细胞-小胶质细胞串扰的重要性，以及其在长期脑改变中的参与，这些改变是由产前mHFD在不同性别的后代中引起的。mHFD特别在雄性青少年后代中诱导髓鞘形成变化。mHFD增加了男女青少年后代的小胶质细胞-突触接触。mHFD减少两种性别的青少年后代中的小胶质细胞成熟溶酶体。mHFD在青春期损害社会新奇感和感觉运动门控。
Prenatal exposure to maternal high-fat diet (mHFD) acts as a risk factor for various neurodevelopmental alterations in the progeny. Recent studies in mice revealed that mHFD results in both neuroinflammation and hypomyelination in the exposed offspring. Microglia, the brain-resident macrophages, play crucial roles during brain development, notably by modulating oligodendrocyte populations and performing phagocytosis of myelin sheaths. Previously, we reported that mHFD modifies microglial phenotype (i.e., morphology, interactions with their microenvironment, transcripts) in the hippocampus of male and female offspring. In the current study, we further explored whether mHFD may induce myelination changes among the hippocampal-corpus callosum-prefrontal cortex pathway, and result in behavioral outcomes in adolescent offspring of the two sexes. To this end, female mice were fed with control chow or HFD for 4 weeks before mating, during gestation, and until weaning of their litter. Histological and ultrastructural analyses revealed an increased density of myelin associated with a reduced area of cytosolic myelin channels in the corpus callosum of mHFD-exposed male compared to female offspring. Transcripts of myelination-associated genes including Igf1 –a growth factor released by microglia– were also lower, specifically in the hippocampus (without changes in the prefrontal cortex) of adolescent male mouse offspring. These changes in myelin were not related to an altered density, distribution, or maturation of oligodendrocytes, instead we found that microglia within the corpus callosum of mHFD-exposed offspring showed reduced numbers of mature lysosomes and increased synaptic contacts, suggesting microglial implication in the modified myelination. At the behavioral level, both male and female mHFD-exposed adolescent offspring presented loss of social memory and sensorimotor gating deficits. These results together highlight the importance of studying oligodendrocyte-microglia crosstalk and its involvement in the long-term brain alterations that result from prenatal mHFD in offspring across sexes. mHFD induces myelination changes specifically in male adolescent offspring. mHFD increases microglia-synapse contacts in adolescent offspring of both sexes. mHFD reduces microglial mature lysosomes in adolescent offspring of both sexes. mHFD impairs social novelty and sensorimotor gating during adolescence.
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DOI：
10.1016/j.bbi.2016.08.005
发表时间：
2016-11
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Graf AE;Lallier SW;Waidyaratne G;Thompson MD;Tipple TE;Hester ME;Trask AJ;Rogers LK
通讯作者：
Rogers LK
影响因子：
5.5
作者：
Domingues HS;Portugal CC;Socodato R;Relvas JB
通讯作者：
Relvas JB
影响因子：
32.4
作者：
Filipello, Fabia;Morini, Raffaella;Matteoli, Michela
通讯作者：
Matteoli, Michela
影响因子：
9.3
作者：
El Hajj, Hassan;Savage, Julie C.;Tremblay, Marie-Eve
通讯作者：
Tremblay, Marie-Eve
影响因子：
9.3
作者：
Bordeleau, Maude;Lacabanne, Chloe;Tremblay, Marie-Eve
通讯作者：
Tremblay, Marie-Eve