The present address of Kathryn J. Hilton is the School of Biological Sciences, University of Southampton, Southampton, SO16 7PX, UK.
Neurotrophin-induced preprotachykinin-A gene promoter modulation in organotypic rat spinal cord culture
Article first published online: 26 MAY 2006
Journal of Neurochemistry
Volume 98, Issue 3, pages 690–699, August 2006
How to Cite
Hilton, K. J., Bateson, A. N. and King, A. E. (2006), Neurotrophin-induced preprotachykinin-A gene promoter modulation in organotypic rat spinal cord culture. Journal of Neurochemistry, 98: 690–699. doi: 10.1111/j.1471-4159.2006.03910.x
- Issue published online: 19 JUN 2006
- Article first published online: 26 MAY 2006
- Received November 4, 2005; revised manuscript received February 17, 2006; accepted February 23, 2006.
- spinal cord;
- substance P
To study regulation of the preprotachykinin-A gene promoter, we utilised a biolistic gene transfer protocol to deliver a DNA construct that incorporates a portion of the preprotachykinin-A gene promoter and an enhanced green fluorescent protein reporter gene into neonatal rat spinal cord organotypic slices. The ability of the neurokinin-1 receptor agonist [Sar9,Met(O2)11]-substance P, nerve growth factor and brain derived neurotrophic factor to modulate positively preprotachykinin-A gene promoter construct activity, as indicated by de novo enhanced green fluorescent protein expression, was determined. Treatment of organotypic slices with [Sar9, Met(O2)11]-substance P (10 μm, P < 0.05), nerve growth factor (200 ng/mL, P < 0.001) or brain derived neurotrophic factor (200 ng/mL, P < 0.02) significantly increased the proportion of cytomegaloviral promoter-DsRed transfected cells (used to visualise total transfected cells) that co-expressed enhanced green fluorescent protein. The distribution of enhanced green fluorescent protein/DsRed-positive neurones across spinal laminae was broadly in line with the known distribution of spinal Trk and neurokinin-1 receptors. These data suggest a modulated activity of the preprotachykinin-A gene promoter in spinal neurones in vitro by substance P and/or neurotrophins. The functional consequences of such transcriptional changes within central peptidergic circuitry and their relevance to chronic pain are considered.