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首页> 外文期刊>The European journal of neuroscience. >Abnormal dendritic morphology in the cerebellum of cyclooxygenase-2~ -knockin mice
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Abnormal dendritic morphology in the cerebellum of cyclooxygenase-2~ -knockin mice

机译：Abnormal dendritic morphology in the cerebellum of cyclooxygenase-2~ -knockin mice

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摘要

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 C0X-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 C0X-2~--KI mice cerebellum compared with wild-type (WT) matched controls at postnatal day 25 (P25). We show that C0X-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 C0X-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 C0X-2~--KI mouse model can be used to study a subset of ASD pathologies.

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