INSERM 1141, NeuroDiderot, Neuroprotection of the Developing Brain, Université Paris Cité, 75019 Paris, France.
Service de Psychiatrie de l'Enfant et de l'Adolescent, APHP, Hôpital Robert Debré, 75019 Paris, France.
Int J Mol Sci. 2023 Oct 13;24(20):15139. doi: 10.3390/ijms242015139.
Autism Spectrum Disorder (ASD) is a synaptic disorder with a GABA/glutamate imbalance in the perineuronal nets and structural abnormalities such as increased dendritic spines and decreased long distance connections. Specific pregnancy disorders significantly increase the risk for an ASD phenotype such as preeclampsia, preterm birth, hypoxia phenomena, and spontaneous miscarriages. They are associated with defects in the glycosylation-immune placental processes implicated in neurogenesis. Some glycans epitopes expressed in the placenta, and specifically in the extra-villous trophoblast also have predominant functions in dendritic process and synapse function. Among these, the most important are CD57 or HNK1, CD22, CD24, CD33 and CD45. They modulate the innate immune cells at the maternal-fetal interface and they promote foeto-maternal tolerance. There are many glycan-based pathways of immunosuppression. N-glycosylation pathway dysregulation has been found to be associated with autoimmune-like phenotypes and maternal-autoantibody-related (MAR) autism have been found to be associated with central, systemic and peripheric autoimmune processes. Essential molecular pathways associated with the glycan-epitopes expression have been found to be specifically dysregulated in ASD, notably the Slit/Robo, Wnt, and mTOR/RAGE signaling pathways. These modifications have important effects on major transcriptional pathways with important genetic expression consequences. These modifications lead to defects in neuronal progenitors and in the nervous system's implementation specifically, with further molecular defects in the GABA/glutamate system. Glycosylation placental processes are crucial effectors for proper maternofetal immunity and endocrine/paracrine pathways formation. Glycans/ galectins expression regulate immunity and neurulation processes with a direct link with gene expression. These need to be clearly elucidated in ASD pathophysiology.
自闭症谱系障碍 (ASD) 是一种突触疾病，其周围神经网中存在 GABA/谷氨酸失衡以及结构异常，如树突棘增多和远距离连接减少。特定的妊娠疾病会显著增加 ASD 表型的风险，如子痫前期、早产、缺氧现象和自然流产。它们与神经发生过程中涉及的糖基化-免疫胎盘过程缺陷有关。胎盘表达的一些糖基化表位，特别是绒毛外滋养细胞中也具有树突和突触功能的主要功能。其中最重要的是 CD57 或 HNK1、CD22、CD24、CD33 和 CD45。它们调节母胎界面的固有免疫细胞，并促进胎母耐受。有许多基于聚糖的免疫抑制途径。已经发现 N-糖基化途径的失调与自身免疫样表型有关，并且与母体自身抗体相关的（MAR）自闭症与中枢、全身和外周自身免疫过程有关。与糖基化表位表达相关的重要分子途径已被发现特别是在 ASD 中失调，特别是 Slit/Robo、Wnt 和 mTOR/RAGE 信号通路。这些修饰对具有重要遗传表达后果的主要转录途径有重要影响。这些修饰导致神经元祖细胞和神经系统的实施缺陷，特别是 GABA/谷氨酸系统的进一步分子缺陷。糖基化胎盘过程是适当的母胎免疫和内分泌/旁分泌途径形成的关键效应物。聚糖/半乳糖凝集素的表达调节免疫和神经发生过程，与基因表达直接相关。这些在 ASD 病理生理学中需要明确阐明。
