TY - JOUR

T1 - The C-terminal flanking peptide of neuropeptide Y (NPY) is not essential for seizure-suppressant actions of prepro-NPY overexpression in male rats

AU - Soud, Katia

AU - Jørgensen, Søren Heide

AU - Woldbye, David Paul Drucker

AU - Sørensen, Andreas Toft

PY - 2019

Y1 - 2019

N2 - The full coding sequence of neuropeptide Y (NPY), prepro-NPY, is sequentially metabolized into three peptides; an N-terminus 28-amino acid signaling peptide, the NPY peptide itself (NPY1-36), and a 30-amino acid C-terminus peptide, known as the C-terminal flanking peptide of neuropeptide-Y (CPON). While the signaling peptide directs intracellular trafficking and NPY1-36 is well characterized, the biological function of CPON is unknown. This is noteworthy because CPON is co-stored and co-released along with NPY1-36 and could thus potentially serve important functions. To assess the role of CPON, we adapted a viral genetic approach using two different vector designs encoding NPY, but where the CPON coding sequence was excluded from one of the vectors. Thus, the effect of CPON was indirectly assessed. Male rats received intrahippocampal injections of either a vector encoding NPY1-39 whose metabolism yields NPY1-36 and not CPON, or a prepro-NPY vector encoding both NPY1-36 and CPON. A third vector encoding EGFP served as control. We subsequently studied to what extent CPON might affect seizure susceptibility and memory performance, respectively, to address two important questions to evaluate the potential of NPY gene therapy in epilepsy. Both NPY vectors, as compared to EGFP control, were found to be equally effective at suppressing acute kainate–induced seizures, and both did not influence learning and memory performance in the Morris water maze. Thus CPON itself does not appear to aid actions governed by vector–mediated overexpression of NPY1-36 within the hippocampus. Whether CPON serves other important functions remains to be determined.

AB - The full coding sequence of neuropeptide Y (NPY), prepro-NPY, is sequentially metabolized into three peptides; an N-terminus 28-amino acid signaling peptide, the NPY peptide itself (NPY1-36), and a 30-amino acid C-terminus peptide, known as the C-terminal flanking peptide of neuropeptide-Y (CPON). While the signaling peptide directs intracellular trafficking and NPY1-36 is well characterized, the biological function of CPON is unknown. This is noteworthy because CPON is co-stored and co-released along with NPY1-36 and could thus potentially serve important functions. To assess the role of CPON, we adapted a viral genetic approach using two different vector designs encoding NPY, but where the CPON coding sequence was excluded from one of the vectors. Thus, the effect of CPON was indirectly assessed. Male rats received intrahippocampal injections of either a vector encoding NPY1-39 whose metabolism yields NPY1-36 and not CPON, or a prepro-NPY vector encoding both NPY1-36 and CPON. A third vector encoding EGFP served as control. We subsequently studied to what extent CPON might affect seizure susceptibility and memory performance, respectively, to address two important questions to evaluate the potential of NPY gene therapy in epilepsy. Both NPY vectors, as compared to EGFP control, were found to be equally effective at suppressing acute kainate–induced seizures, and both did not influence learning and memory performance in the Morris water maze. Thus CPON itself does not appear to aid actions governed by vector–mediated overexpression of NPY1-36 within the hippocampus. Whether CPON serves other important functions remains to be determined.

KW - CPON

KW - gene therapy

KW - Hippocampus

KW - learning and memory

KW - Neuropeptide Y (NPY)

KW - seizures

KW - viral vectors

U2 - 10.1002/jnr.24350

DO - 10.1002/jnr.24350

M3 - Journal article

C2 - 30367522

AN - SCOPUS:85055540637

VL - 97

SP - 362

EP - 372

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 3

ER -