Abnormal dendritic morphology in the cerebellum of cyclooxygenase-2− knockin mice,European Journal of Neuroscience

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Abnormal dendritic morphology in the cerebellum of cyclooxygenase-2− knockin mice
European Journal of Neuroscience ( IF 2.7 ) Pub Date : 2021-09-12 , DOI: 10.1111/ejn.15454
Ashby Kissoondoyal _{1,

2} , Ravneet Rai-Bhogal _{2,

3} , Dorota A Crawford _{1,

2,

3}

Affiliation

Prostaglandin E2 (PGE2) is a bioactive signalling molecule metabolized from the phospholipid membranes by the enzymatic activity of cycloxygenase-2 (COX-2). In the developing brain, COX-2 constitutively regulates the production of PGE2, which is important in neuronal development. However, abnormal COX-2/PGE2 signalling has been linked to neurodevelopmental disorders including autism spectrum disorders (ASDs). We have previously demonstrated that COX-2⁻-KI mice show autism-related behaviours including social deficits, repetitive behaviours and anxious behaviours. COX-2-deficient mice also have deficits in pathways involved in synaptic transmission and dendritic spine formation. In this study, we use a Golgi–COX staining method to examine sex-dependent differences in dendritic and dendritic spine morphology in neurons of COX-2⁻-KI mice cerebellum compared with wild-type (WT) matched controls at postnatal day 25 (P25). We show that COX-2⁻-KI mice have increased dendritic arborization closer to the cell soma and increased dendritic looping. We also observed a sex-dependent effect of the COX-2⁻-KI on dendritic thickness, dendritic spine density, dendritic spine morphology, and the expression of β-actin and the actin-binding protein spinophilin. Our findings show that changes in COX-2/PGE2 signalling lead to impaired morphology of dendrites and dendritic spines in a sex-dependant manner and may contribute the pathology of the cerebellum seen in individuals with ASD. This study provides further evidence that the COX-2⁻-KI mouse model can be used to study a subset of ASD pathologies.

中文翻译：

环氧合酶2-敲入小鼠小脑树突形态异常

前列腺素 E2 (PGE2) 是一种生物活性信号分子，通过 cycloxygenase-2 (COX-2) 的酶活性从磷脂膜代谢。在发育中的大脑中，COX-2 组成性地调节 PGE2 的产生，这在神经元发育中很重要。然而，异常的 COX-2/PGE2 信号传导与包括自闭症谱系障碍 (ASD) 在内的神经发育障碍有关。我们之前已经证明 COX-2 ^--KI 小鼠表现出与自闭症相关的行为，包括社交缺陷、重复行为和焦虑行为。COX-2 缺陷小鼠在涉及突触传递和树突棘形成的通路中也存在缺陷。在这项研究中，我们使用高尔基体-COX 染色方法来检查 COX-2 ^- -KI 小鼠小脑神经元中树突和树突棘形态的性别依赖性差异，与出生后第 25 天的野生型 (WT) 匹配对照相比。第 25 页）。我们表明，COX-2 ^- -KI 小鼠在靠近细胞胞体的地方增加了树突树枝状化，并增加了树突环。我们还观察到 COX-2 的性别依赖性效应^--KI对树突厚度、树突棘密度、树突棘形态以及β-肌动蛋白和肌动蛋白结合蛋白spinophilin的表达。我们的研究结果表明，COX-2/PGE2 信号传导的变化以性别依赖的方式导致树突和树突棘的形态受损，并可能导致 ASD 患者的小脑病理。本研究进一步证明 COX-2 ^- -KI 小鼠模型可用于研究 ASD 病理的一个子集。

更新日期：2021-10-20

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