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Adverse events at critical stages of development can lead to lasting dysfunction in the central nervous system (CNS). To seek potential underlying changes in synaptic function, we used a newly developed protocol to measure alterations in receptor-mediated Ca2+ fluorescence responses of synaptoneurosomes, freshly isolated from selected regions of the CNS concerned with emotionality and pain processing. We compared adult male controls and offspring of rats exposed to social stress in late pregnancy (prenatal stress, PS), which showed programmed behavioural changes indicating anxiety, anhedonia and pain hypersensitivity. We found corresponding increases, in PS rats compared with normal controls, in responsiveness of synaptoneurosomes from frontal cortex to a glutamate receptor (GluR) agonist, and from spinal cord to activators of nociceptive afferents. Through a combined pharmacological and biochemical strategy, we found evidence for a role of phospholipase D1 (PLD1)-mediated signalling, that may involve 5-HT2A receptor (5-HT2AR) activation, at both levels of the nervous system. These changes might participate in underpinning the enduring alterations in behaviour induced by PS.
|Number of pages||7|
|Journal||International Journal of Biochemistry and Cell Biology|
|Early online date||7 Aug 2013|
|Publication status||Published - Nov 2013|
5α-reduced neurosteroids sex-dependently reverse central prenatal programming of neuroendocrine stress responses in ratsBrunton, P. J., Donadio, M. V., Yao, S. T., Greenwood, M., Seckl, J. R., Murphy, D. & Russell, J. A., 14 Jan 2015, In: Journal of Neuroscience. 35, 2, p. 666-677
Research output: Contribution to journal › Article › peer-reviewOpen AccessFile