Phospholipase D-mediated hypersensitivity at central synapses is associated with abnormal behaviours and pain sensitivity in rats exposed to prenatal stress.
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 Ca(2+) 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.
Centre for Integrative Physiology, School of Biomedical Sciences, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, UK.
Liting
L
Sun
Hayley L
HL
Gooding
Paula J
PJ
Brunton
John A
JA
Russell
Rory
R
Mitchell
Sue
S
Fleetwood-Walker
D000818:Animals; D001522:Behavior, Animal; D002540:Cerebral Cortex / Q000473:pathology; D005260:Female; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D006967:Hypersensitivity / Q000150:complications / Q000201:enzymology / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D059225:Nociception / Q000187:drug effects; D010146:Pain / Q000150:complications / Q000201:enzymology* / Q000473:pathology / Q000523:psychology*; D010739:Phospholipase D / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D013315:Stress, Psychological / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D013569:Synapses / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology
D044402:Receptor, Serotonin, 5-HT2A; D006710:Homocysteine; C007956:homocysteic acid; D010739:Phospholipase D; C106801:phospholipase D1
5-HT(2A) receptor; Nociception; Phospholipase D; Prenatal stress; Synaptoneurosomes