Prostaglandin E2 Increases Neurite Length and the Formation of Axonal Loops, and Regulates Cone Turning in Differentiating NE4C Cells Via PKA

Kissoondoyal, Ashby; Crawford, Dorota A.

doi:10.1007/s10571-020-01029-4

Cited by 6 publications

(18 citation statements)

References 74 publications

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“…We have previously demonstrated that PGE2 can increase neurite length of differentiating NE4C stem cells through PKA‐dependent mechanisms (Kissoondoyal & Crawford, 2021). Findings from other groups showed that local injection of PGE2 into the rat cerebellum at postnatal day 10 (PN10) and PN12 reduced dendritic length in both adult males and females (Dean, Wright, et al, 2012).…”

Section: Resultsmentioning

confidence: 99%

“…We have previously demonstrated in vitro that exposure to PGE2 throughout differentiation of NE‐4C stem cells significantly increased the proportion of neurites that formed loops (Kissoondoyal & Crawford, 2021). Here, we examine for the first time the proportion of neurites forming dendritic loops in an in vivo model.…”

Section: Resultsmentioning

confidence: 99%

“…We examined the odds that any given neurite would form a dendritic loop. The greatest exterior angle of all neurites measured was determined, and any neurite with an angle above 270° was classified as forming a dendritic loop as we have previously described (Kissoondoyal & Crawford, 2021) (methods; Figure 5). When this distinction was made, there were visible differences in the distribution of neurites forming dendritic loops between WT and COX‐2 − ‐KI mice (males and females combined) with a denser distribution of loops in COX‐2 − ‐KI mice (Figure 5).…”

Section: Resultsmentioning

confidence: 99%

“…Concentric circles were generated by the software every 10 μm from a point made at the centre of the soma of each cell, and the number of intersecting neurites were computed (Binley et al, 2014). Although normally quantified subjectively, we used a quantitative method to determine self-fasciculating or looping dendrites as described in (Kissoondoyal & Crawford, 2021). Using the traced neurites from the Simple Neurite Tracer plugin, the maximum angle from each neurite was used to classify each neurite as looping or non-looping.…”

Section: Sholl Analysis and Dendritic Loop Quantificationmentioning

confidence: 99%

“…Using the traced neurites from the Simple Neurite Tracer plugin, the maximum angle from each neurite was used to classify each neurite as looping or non-looping. If the angle for a given neurite exceeded 270 , the neurite was classified as a loop as we previously described (Kissoondoyal & Crawford, 2021).…”

Section: Sholl Analysis and Dendritic Loop Quantificationmentioning

confidence: 99%

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Abnormal dendritic morphology in the cerebellum of cyclooxygenase‐2⁻ knockin mice

Kissoondoyal

Rai-Bhogal

Crawford

2021

Eur J of Neuroscience

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

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Sholl Analysis and Dendritic Loop Quantificationmentioning

confidence: 99%

Section: Sholl Analysis and Dendritic Loop Quantificationmentioning

confidence: 99%

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Abnormal dendritic morphology in the cerebellum of cyclooxygenase‐2⁻ knockin mice

Kissoondoyal

Rai-Bhogal

Crawford

2021

Eur J of Neuroscience

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Emerging trends on nanomaterial-based simultaneous electrochemical sensing of dopamine and acetaminophen

Roy,

Chakravorty,

Mini

et al. 2024

Results in Chemistry

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Maternal exposure to prostaglandin e2 results in abnormal dendritic morphology in the cerebellum and related motor behaviour in mouse offspring

Kissoondoyal,

Ho,

Wong

et al. 2023

Preprint

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The lipid signalling molecule prostaglandin E2 (PGE2) is important in healthy brain development. Abnormal PGE2 levels during prenatal development, which can be influenced by genetic causes and exposure to various environmental risk factors, have been linked to increased prevalence of Autism Spectrum Disorders (ASDs). Growing research in animal models aims to provide evidence for the mechanisms by which increased or reduced PGE2 levels influence brain development. In this study, we show that maternal exposure to PGE2 in mice at gestational day 11 (G11) results in molecular changes within the cerebellum and associated behaviours in offspring. We observed a decrease in cerebellar cell density originating at G11 (in males and females) and at G16 (in females only). In Golgi-COX-stained cerebellar slices from PGE2-exposed offspring at the postnatal day 30 (PN30), we found an increase in dendritic arborization, the odds of observing dendritic loops, dendritic spine density, and the odds of observing mature (mushroom-shaped) spines. We also observed a decrease in the expression level of the cytoskeletal protein beta-actin, the actin associated protein spinophilin, and the cell adhesion protein N-Cadherin. In addition, we found that specifically PGE2-exposed male offspring exhibited abnormal cerebellar related motor function. This study adds further evidence that changes in the PGE2 levels during critical times may impact the developing brain differently in males and females. These findings also emphasize the importance of examining sex differences in research relevant to neurodevelopmental disorders.

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Prostaglandin E2 Increases Neurite Length and the Formation of Axonal Loops, and Regulates Cone Turning in Differentiating NE4C Cells Via PKA

Cited by 6 publications

References 74 publications

Abnormal dendritic morphology in the cerebellum of cyclooxygenase‐2⁻ knockin mice

Abnormal dendritic morphology in the cerebellum of cyclooxygenase‐2⁻ knockin mice

Emerging trends on nanomaterial-based simultaneous electrochemical sensing of dopamine and acetaminophen

Maternal exposure to prostaglandin e2 results in abnormal dendritic morphology in the cerebellum and related motor behaviour in mouse offspring

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Prostaglandin E2 Increases Neurite Length and the Formation of Axonal Loops, and Regulates Cone Turning in Differentiating NE4C Cells Via PKA

Cited by 6 publications

References 74 publications

Abnormal dendritic morphology in the cerebellum of cyclooxygenase‐2− knockin mice

Abnormal dendritic morphology in the cerebellum of cyclooxygenase‐2− knockin mice

Emerging trends on nanomaterial-based simultaneous electrochemical sensing of dopamine and acetaminophen

Maternal exposure to prostaglandin e2 results in abnormal dendritic morphology in the cerebellum and related motor behaviour in mouse offspring

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Abnormal dendritic morphology in the cerebellum of cyclooxygenase‐2⁻ knockin mice

Abnormal dendritic morphology in the cerebellum of cyclooxygenase‐2⁻ knockin mice