title: Prostaglandin E2 is an endogenous modulator of cerebellar development and complex behavior during a sensitive postnatal period.
abstract: 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.
authors.affiliation: Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Dean
authors.forename: Jessica F
authors.initials: JF
authors.lastname: Knutson
authors.forename: Desiree L
authors.initials: DL
authors.lastname: Krebs-Kraft
authors.forename: Margaret M
authors.initials: MM
authors.lastname: McCarthy
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D002452:Cell Count; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects / Q000648:ultrastructure; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D007276:Injections, Intraventricular / Q000379:methods; D007279:Injections, Subcutaneous; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009924:Organ Culture Techniques; D010988:Play and Playthings; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D011689:Purkinje Cells / Q000166:cytology / Q000502:physiology; D051381:Rats; D012044:Regression Analysis; D012684:Sensory Thresholds / Q000187:drug effects / Q000502:physiology; D012737:Sex Factors; D016622:Silver Staining; D013997:Time Factors; D000099273:Neurabins
chemical_list: D015232:Dinoprostone; D004791:Enzyme Inhibitors; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D000099273:Neurabins