Neurotrophic and neuroprotective effects of pituitary adenylate cyclase-activating polypeptide (pACAP) on mesencephalic dopaminergic neurons

Abstract

The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is present in many regions of the adult and developing brain as are receptors for PACAP. PACAP stimulates different signalling cascades in neurons, involving cAMP, MAP kinase, and calcium. These characteristics suggest that PACAP may influence neuronal development. Here we have studied the effects of PACAP on mesencephalic dopaminergic neurons using primary cultures from embryonic rats. PACAP increased the number of tyrosine hydroxylase (TH)-immunoreactive neurons, elevated TH protein, and enhanced tritiated dopamine uptake in these cultures. Moreover, PACAP counteracted the effects of 6-hydroxydopamine treatments, which induce cell death of dopaminergic neurons. In situ hybridisation showed that both PACAP and PACAP receptor type 1 are present in developing and adult rat mesencephalon. These results show that PACAP has a neurotrophic action on dopaminergic neurons and partially protects them against 6-OHDA induced neurotoxicity.

Pituitary adenylate cyclase activating peptide-27 – like immunoreactive nerve fibers in the mucosal layer of canine gastrointestinal tract in physiology and during inflammatory bowel disease

“…The density backward declines and the smallest number of such fibers is observed in descending colon. It suggests that the exact functions of PACAP in canine digestive tract under physiological conditions are different in particular segments of intestines, what is in agreement with previous studies on other species (19,29,30).…”

“…As a result they confirm previous studies, where expression of PACAP has been described in the GI tract of various species, including humans (8,10,14,19,20), and suggest that also in dog this peptide plays, known in other species, important multiple biological functions for optimal functioning of the gastrointestinal tract. Its role has been shown in processes, such as the gut motility, regulation of neurotransmitter release, as well as secretion of the gastric and intestinal glands (6,19,29,30). On the other hand, in spite of the fact of well-established function of PACAP in the GI tract (19), the number of the enteric PACAP-27-LI neurons under physiological conditions generally noted in the study was relatively low, especially in small and large intestine, what confirms previous studies, which demonstrated that PACAP is the predominant form in mammalian tissues (19).…”

“…It is well-known that injury to neurons causes an increase in the expression of neurotransmitters, which promote the regeneration of injured cells. Previous studies have documented the ability of PACAP to prevent apoptotic cell death and protect cortical neurons against glutamate-induced cytotoxity, dopaminergic neurons against 6-hydroxydopamine-induced cytotoxicity, cerebellar granule neurons against ethanol, an oxidative stress inducing cell death, as well as cerebral neurons during ischaemia (28)(29)(30). It is also known that PACAP (mainly via PAC1 receptor) affects proliferation of neurons, axon regeneration, and development of the nervous system (3).…”

PACAP38 increases vesicular monoamine transporter 2 (VMAT2) expression and attenuates methamphetamine toxicity

“…Additionally, PACAP38 can attenuate neuronal damage from 6-hydroxydopamine (6-OHDA), a Parkinson's disease model toxicant, when administered to primary mesencephalic cultures or co-infused into the substantia nigra of adult rats (Takei, et al 1998, Reglodi, et al 2004b). Since PACAP38 has been shown to be neuroprotective against 6-OHDA, we decided to examine the effects of PACAP38 on the neurotoxicity of systemically-administered methamphetamine (METH).…”

Class II G Protein-Coupled Receptors and Their Ligands in Neuronal Function and Protection

“…Most of the actions of PACAP on cortical neurons are mediated through the cAMP pathway (Martin et al, 1995;Morio et al, 1996) although it has been reported that PACAP can directly modulate N-methyl-D-aspartate receptors independently of intracellular second messengers (Liu and Madsen, 1997). In cortical neurons, PACAP can also prevent the neurotoxic effect of other insults such as lipopolysaccharide (Kong et al, 1999), and in mesencephalic dopaminergic neurons PACAP can counteract the neurotoxic effect of 6-hydroxydopamine (Takei et al, 1998). In a study relevant to AD, it was shown that PACAP can protect PC12 cells against death induced by amyloid β-peptide (Onoue et al, 2002).…”