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Regulation of VIP and other Neuropeptides by c‐Jun in Sensory Neurons: Implications for the Neuropeptide Response to Axotomy
Author(s) -
Mulderry Peter K.,
Dobson Stephen P.
Publication year - 1996
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1996.tb01542.x
Subject(s) - galanin , axotomy , vasoactive intestinal peptide , neuropeptide , biology , transcription factor , microbiology and biotechnology , medicine , gene expression , endocrinology , gene , central nervous system , receptor , biochemistry
Peripheral axotomy of adult rat sensory neurons causes induction of the transcription factor c‐Jun and increased expression of the neuropeptides vasoactive intestinal polypeptide (VIP), galanin and neuropeptide Y. To determine whether VIP induction is dependent on transcriptional regulation by c‐Jun, we exploited the fact that c‐Jun and VIP are also induced in cultured sensory neurons. We blocked c‐Jun synthesis by microinjecting antisense oligonucleotides and found that VIP expression, determined by quantitative immunofluorescence, was specifically reduced. Blockade of c‐Jun expression also resulted in reduced neuropeptide Y expression but left galanin, substance P and calcitonin gene‐related peptide unaffected. Since in vitro electrophoretic mobility shift assays showed that a nominal cyclic AMP responsive element (CRE) associated with the rat VIP gene could bind c‐Jun‐containing transcription factor complexes, we next investigated whether VIP expression in sensory neurons might depend on transcription factor binding to the CRE. When a DNA plasmid containing multiple copies of the CRE was injected into newly cultured sensory neurons to sequester transcription factors binding the endogenous CRE, there was a selective reduction in VIP expression. VIP induction in sensory neurons therefore probably results from transcriptional activation by c‐Jun acting in combination with other factor(s), possibly acting through the CRE. These results show that c‐Jun can regulate transcription of other genes affected by axotomy and imply that it could be a key regulator of the neuronal axotomy response.