S.L.D. and J.F.K. contributed equally to this work.
Prostaglandin E2 is an endogenous modulator of cerebellar development and complex behavior during a sensitive postnatal period
Article first published online: 18 APR 2012
© 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 35, Issue 8, pages 1218–1229, April 2012
How to Cite
Dean, S. L., Knutson, J. F., Krebs-Kraft, D. L. and McCarthy, M. M. (2012), Prostaglandin E2 is an endogenous modulator of cerebellar development and complex behavior during a sensitive postnatal period. European Journal of Neuroscience, 35: 1218–1229. doi: 10.1111/j.1460-9568.2012.08032.x
- Issue published online: 18 APR 2012
- Article first published online: 18 APR 2012
- Received 6 September 2011, revised 3 January 2012, accepted 11 January 2012
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.