Delayed up-regulation of Zac1 and PACAP type I receptor after transient focal cerebral ischemia in mice.
The Zac1 gene encodes a zinc finger protein that regulates both apoptosis and cell cycle arrest in vitro. Furthermore, Zac1 protein seems to trans-activate the gene encoding the type I receptor for pituitary adenylate cyclase activating polypeptide (PACAP). Northern blot analysis revealed high levels of Zac1 mRNA in the rodent brain. In the present study, we demonstrate by in situ hybridization histochemistry a progressive increase in Zac1 transcripts in the mouse brain from day 1 to day 3 following transient focal cerebral ischemia. Moreover, we observed an up-regulation of PACAP type I receptor mRNA expression showing a similar temporospatial distribution. Late induction of cell death promoting Zac1 in the post-ischemic brain may be attributed to delayed or secondary cell death. Co-induction of the type I receptor for neurotrophic PACAP however, points to a role in restorative processes.