7 research outputs found
Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) and Its Receptors Are Present and Biochemically Active in the Central Nervous System of the Pond Snail Lymnaea stagnalis
PACAP is a highly conserved adenylate cyclase (AC) activating polypeptide, which, along with its receptors (PAC1-R, VPAC1, and VPAC2), is expressed in both vertebrate and invertebrate nervous systems. In vertebrates, PACAP has been shown to be involved in associative learning, but it is not known if it plays a similar role in invertebrates. To prepare the way for a detailed investigation into the possible role of PACAP and its receptors in a suitable invertebrate model of learning and memory, here, we undertook a study of their expression and biochemical role in the central nervous system of the pond snail Lymnaea stagnalis. Lymnaea is one of the best established invertebrate model systems to study the molecular mechanisms of learning and memory, including the role of cyclic AMP-activated signaling mechanisms, which crucially depend on the learning-induced activation of AC. However, there was no information available on the expression of PACAP and its receptors in sensory structures and central ganglia of the Lymnaea nervous system known to be involved in associative learning or whether or not PACAP can actually activate AC in these ganglia. Here, using matrix-assisted laser desorption ionization time of flight (MALDI-TOF) and immunohistochemistry, we established the presence of PACAP-like peptides in the cerebral ganglia and the lip region of Lymnaea. The MALDI-TOF data indicated an identity with mammalian PACAP-27 and the presence of a squid-like PACAP-38 highly homologous to vertebrate PACAP-38. We also showed that PACAP, VIP, and maxadilan stimulated the synthesis of cAMP in Lymnaea cerebral ganglion homogenates and that this effect was blocked by the appropriate general and selective PACAP receptor antagonists
Posttraumatic Administration of Pituitary Adenylate Cyclase Activating Polypeptide in Central Fluid Percussion Injury in Rats
Several in vitro and in vivo experiments have
demonstrated the neuroprotective effects of pituitary
adenylate cyclase activating polypeptide
(PACAP) in focal cerebral ischemia, Parkinson's
disease and traumatic brain injury (TBI). The
aim of the present study was to analyze the effect
of PACAP administration on diffuse axonal
injury (DAI), an important contributor to morbidity
and mortality associated with TBI, in a
central fluid percussion (CFP) model of TBI.
Rats were subjected to moderate (2 Atm) CFP
injury. Thirty min after injury, 100 渭g PACAP
was administered intracerebroventricularly.
DAI was assessed by immunohistochemical
detection of 尾-amyloid precursor protein, indicating
impaired axoplasmic transport, and
RMO-14 antibody, representing foci of cytoskeletal
alterations (neurofilament compaction),
both considered classical markers of axonal
damage. Analysis of damaged, immunoreactive
axonal profiles revealed significant axonal protection
in the PACAP-treated versus vehicletreated
animals in the corticospinal tract, as far
as traumatically induced disturbance of axoplasmic
transport and cytoskeletal alteration were
considered. Similarly to our former observations
in an impact acceleration model of diffuse TBI,
the present study demonstrated that PACAP
also inhibits DAI in the CFP injury model. The
finding indicates that PACAP and derivates can
be considered potential candidates for further
experimental studies, or purportedly for clinical
trials in the therapy of TBI