Axotomy-induced changes in pituitary adenylate cyclase activating polypeptide (PACAP) and PACAP receptor gene expression in the adult rat facial motor nucleus

Abstract

It has been demonstrated that pituitary adenylate cyclase activating polypeptide (PACAP) promotes the survival of neurons in culture and can inhibit neuronal cell death after experimental injury. Furthermore, peripheral axotomy results in increased PACAP gene expression in sensory and sympathetic neurons, suggesting that PACAP might be a mediator in the injury response in certain parts of the nervous system. However, changes in PACAP expression have not been reported in injured motor neurons, despite the significant problem of motor neuron degeneration in injury and in several neurological diseases. We examined here changes in gene expression of PACAP and two high-affinity PACAP receptors, PAC(1) and VPAC(2), in adult rat motor neurons after facial nerve axotomy by in situ hybridization. PACAP gene expression was very low in facial motor neurons of normal rats. However, a robust time-dependent increase in PACAP mRNA was observed in the facial motor nucleus in most or all axotomized motor neurons. This induction was detectable 6 hr after axotomy, and peaked at 48 hr, when expression on the injured side averaged more than 20-fold higher than that on the contralateral side. Thereafter, PACAP mRNA levels decreased slightly, but remained more than 10-fold elevated for as long as 30 days after axotomy. In contrast to PACAP, gene expression for both the PAC(1) and VPAC(2) receptor was high in facial motor neurons of normal rats. No significant change was observed for VPAC(2) receptor gene expression in facial motor neurons after axotomy, whereas gene expression for the PAC(1) receptor became significantly decreased. The results indicate that the PACAP ligand receptor system is tightly regulated in the facial motor nucleus after axotomy, providing evidence that PACAP may be involved in motor injury responses.

Expression of PACAP-Like Compounds During the Caudal Regeneration of the Earthworm Eisenia fetida

“…Similar increased expression of PACAP has been found by other studies (Jongsma et al 2000). Transection of other nerves also leads to increased PACAP expression, as it has been observed in the mesencephalic trigeminal nucleus after the transection of the masseteric nerve (Larsen et al 1997), in the facial nucleus after axotomy (Zhou et al 1999), and in the superior cervical ganglion after sympathetic postganglionic axotomy (Moller et al 1997). Upregulation of PACAP in nerve cells has been observed not only after mechanical transection of nerves but also after inflammation (Zhang et al 1998).…”

Expression of pituitary adenylate cyclase-activating polypeptide (PACAP) and the PACAP-selective receptor in cultured rat astrocytes, human brain tumors, and in response to acute intracranial injury

“…Altered PACAP or PAC1-R mRNA expression in local circuit neurons in the lesion penumbra, callosal neurons in the contralateral cortex, and thalamic afferents was not observed. Since PAC1-R expression is not always upregulated following injury (Skoglösa et al 1999;Zhou et al 1999), PACAP may exerts its activity through binding VIP receptors. While the present study only investigated the expression at the mRNA level, PACAP release may be increased in response to injury even in the absence of increased mRNA as reported for other neuropeptides (Ma and Bisby 1999).…”

Comparative Examination of Inner Ear in Wild Type and Pituitary Adenylate Cyclase Activating Polypeptide (PACAP)-Deficient Mice

“…PACAP protects neurons against different toxic agents, such as 6-hydroxydopamine, ethanol, oxidative stress, and anisomycin Somogyvari-Vigh and Reglodi 2004;Vaudry et al 2009), but also non-neuronal cells, such as endothelial cells, cardiomyocytes, and kidney cells (Gasz et al 2006;Horvath et al 2010;Racz et al 2007). Endogenous PACAP and its receptors are upregulated after focal and global ischemia (Gillardon et al 1998;Riek-Burchardt et al 2010;Shin et al 2001;Stumm et al 2007), traumatic brain injury and different nerve injuries (Larsen et al 1997;Moller et al 1997;Skoglosa et al 1999;Zhang et al 1996Zhang et al , 1998Zhou et al 1999). Vaudry et al (2005) were the first to show that granule cells from PACAP-deficient mice react to cellular stressors such as ethanol and oxidative stress with higher sensitivity.…”