About this Research Topic
Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP), Vasoactive Intestinal Peptide (VIP) and related peptides, initially identified as endocrine regulators, are widely expressed in the central nervous system where they function as neurotrophic and neuroprotective factors. PACAP, VIP and related peptides act on specific and shared receptors coupled to several transduction signaling pathways including adenylate cyclase and phospholipase C. In the brain, PACAP, VIP and related peptides behave as modulators of synaptic transmission and plasticity, particularly in the hippocampus, a brain area crucially involved in learning and memory. In the hippocampus of rodents, PACAP- and VIP-containing neurons have been identified and all PACAP/VIP receptor subtypes (PAC1, VPAC1 and VPAC2) are expressed, with different localization on neurons and pre-synaptic terminals.
PACAP and VIP exert a complex modulation of AMPA- and NMDA receptors mediated glutamatergic transmission and long-term synaptic plasticity in rat and mouse hippocampus, suggesting an important role of these neuropeptides in learning and memory. Indeed, long-term synaptic plasticity of glutamate-mediated synaptic transmission represents the cellular basis of memory and is disrupted in animal models of cognitive deficits.
Very recent publications have shown rescue effects of PACAP, VIP and related peptides on learning and memory in animal models of diseases involving cognitive deficits, among which Alzheimer's, Huntington and Parkinson diseases. These results open new interesting questions concerning the role of PACAP, VIP and related peptide receptors on learning in health and disease. Are the brain expression level and/or functional properties of PACAP, VIP and related peptide receptors altered in learning disabilities? Can PACAP, VIP and related peptide receptors become a therapeutic target for cognitive deficits? In this respect, it would be important to define the most suitable administration route for PACAP, VIP and related peptides to be used as pharmacological tools. PACAP is able to cross the blood-brain barrier (BBB) and reach the brain after intravenous administration; on the other hand, carrier vesicles have been proposed for brain delivery of VIP. Another promising strategy for brain delivery of PACAP and VIP is intranasal administration. Alternatively, are small-molecule agonists/antagonists of PACAP, VIP and related peptide receptors available for oral administration?
The scope of this Research Topic is to clarify whether pharmacological activation of PACAP, VIP and related peptide receptors might be clinically useful for the treatment of cognition deficits. We are seeking contributions (Original Research articles or Reviews) of either pre-clinical studies on animal models or clinical studies on human patients. Particular attention will be given to articles providing information on:
1) Brain expression level of PAC1/VPAC/secretin/glucagon receptors in animal models of cognitive diseases and/or in human patients with learning deficits;
2) PAC1/VPAC/secretin/glucagon receptor-mediated rescue of synaptic plasticity and/or learning in animal models of cognitive diseases;
3) Synthesis and biological characterization of novel small molecules with drug-like properties acting as agonists or antagonists of PAC1/VPAC/secretin/glucagon receptors.
We will also welcome articles presenting how research on PACAP, VIP and related peptides led to the identification of new targets for the treatment of cognition deficits.
Keywords: PACAP, VIP, Synaptic plasticity, Learning, Cognition deficit
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.