Prostaglandin E2 is an endogenous modulator of cerebellar development and complex behavior during a sensitive postnatal period
Open accessAbstract
Prostaglandins are lipid‐derived molecules that mediate the generation of fever in the central nervous system. In addition to their proinflammatory role, prostaglandins also impact neuronal development and synaptic plasticity, sometimes in a sex‐specific manner. The cerebellum has a high expression of prostaglandin receptors during development, but the role that these molecules play during normal cerebellar maturation is unknown. We demonstrate here that disrupting prostaglandin synthesis with cyclo‐oxygenase inhibitors during a time‐sensitive window in early postnatal life alters cerebellar Purkinje cell development in rats, resulting in initially increased dendritic growth in both sexes. We show that this results in later cerebellar atrophy in males only, resulting in a sex‐specific loss of cerebellar volume. Further, although performance in motor tasks is spared, social interaction and the sensory threshold are altered in males developmentally exposed to cyclo‐oxygenase inhibitors. This work demonstrates a previously unknown role for prostaglandins in cerebellar development and emphasizes the role that the cerebellum plays outside motor tasks, in cognitive and sensory domains that may help to explain its connection to complex neurodevelopmental disorders such as autism.
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Disruption of estrogen synthesis within the developing cerebellum during the second postnatal week reduces play by juvenile males.
“Lastly, we have found that disruption of estrogen synthesis within the developing cerebellum during a later sensitive period, the second postnatal week, reduces play by juvenile males (Dean et al., 2012).”
From Developmental origins of sex differences in the neural circuitry of play (2020) · cites this paper as Dean et al., 2012
The Results (page unavailable) report that systemic nimesulide treatment from PN7 to PN13 reduced play in juvenile male rats. But the treatment inhibited prostaglandin synthesis, not estrogen synthesis; the Discussion says the relationship between prostaglandins and estradiol in the cerebellum remains for future work. (LLM, conf=0.88)
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- Authors
- Dean, S. L., Knutson, J. F., Krebs‐Kraft, D. L., & McCarthy, M. M.
- Affiliations
- University of Maryland, Baltimore (US)
- Corresponding author
- McCarthy, Margaret M.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2012-04
- Volume
- 35
- Issue
- 8
- Pages
- 1218-1229
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- PMC
- PMC3534986
- OpenAlex
- W1507094742
- Cited by
- 70
- References
- 72
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2023: 9 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 4 · 2018: 5 · 2017: 7 · 2016: 13 · 2015: 4 · 2014: 1 · 2013: 2 · 2012: 1
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (2t32ns063391-21)
- National Institute of Mental Health (R01-MH-52716, R01MH091424, R01MH052716)
- National Institute of General Medical Sciences (T32 GM081810, R15GM081810)
- National Institute of Neurological Disorders and Stroke (T32 NS07375, T32NS007375, T32-NS063391, 5-T32 NS063391-01)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- prostaglandin E2, cerebellar development, Purkinje cells, cyclooxygenase inhibitors, postnatal development, sex differences, cerebellar atrophy, dendritic growth, social interaction, sensory threshold, autism spectrum disorder, neurodevelopmental disorders, prostaglandin receptors
- MeSH terms
- Neurabins, Age Factors, Analysis of Variance, Animals, Animals, Newborn, Behavior, Animal, Cell Count, Cerebellum, Dendrites, Dose-Response Relationship, Drug, Enzyme Inhibitors, Exploratory Behavior, Female, Injections, Intraventricular, Injections, Subcutaneous, Male, Microfilament Proteins, Nerve Tissue Proteins, Organ Culture Techniques, Play and Playthings, Psychomotor Performance, Purkinje Cells, Regression Analysis, Sensory Thresholds, Sex Factors, Time Factors, Dinoprostone, Silver Staining, Rats
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