Abnormal dendritic morphology in the cerebellum of cyclooxygenase‐2 − knockin mice
| Autor: | Ashby Kissoondoyal, Ravneet Rai-Bhogal, Dorota A. Crawford |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
chemistry.chemical_classification
0303 health sciences Cerebellum Dendritic spine General Neuroscience Phospholipid Neurotransmission Biology Cell biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Enzyme medicine.anatomical_structure chemistry medicine biology.protein Cyclooxygenase Prostaglandin E2 030217 neurology & neurosurgery Actin 030304 developmental biology medicine.drug |
| Zdroj: | European Journal of Neuroscience. 54:6355-6373 |
| ISSN: | 1460-9568 0953-816X |
| DOI: | 10.1111/ejn.15454 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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