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

被引:6
|
作者
Soud, Katia [1 ]
Jorgensen, Soren Heide [2 ]
Woldbye, David Paul Drucker [1 ]
Sorensen, Andreas Toft [2 ]
机构
[1] Univ Copenhagen, Dept Neurosci, Lab Neural Plast, Copenhagen, Denmark
[2] Univ Copenhagen, Dept Neurosci, Neuropharmacol & Genet Lab, Copenhagen, Denmark
关键词
CPON; gene therapy; Hippocampus; learning and memory; Neuropeptide Y (NPY); seizures; viral vectors; RECTIFYING POTASSIUM CURRENT; GENE-THERAPY; SYNAPTIC-TRANSMISSION; VIRAL VECTORS; HIPPOCAMPUS; RECEPTORS; EXPRESSION; MODEL; ANTICONVULSANT; IMPAIRMENT;
D O I
10.1002/jnr.24350
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:362 / 372
页数:11
相关论文
共 15 条
  • [1] COLOCALIZATION OF NEUROPEPTIDE TYROSINE (NPY) AND ITS C-TERMINAL FLANKING PEPTIDE (C-PON)
    GULBENKIAN, S
    WHARTON, J
    HACKER, GW
    VARNDELL, IM
    BLOOM, SR
    POLAK, JM
    PEPTIDES, 1985, 6 (06) : 1237 - 1243
  • [2] NEUROPEPTIDE-Y (NPY) AND C-FLANKING PEPTIDE OF NPY IN THE PINEAL-GLAND OF NORMAL AND GANGLIONECTOMIZED SHEEP
    COZZI, B
    MIKKELSEN, JD
    RAVAULT, JP
    MOLLER, M
    JOURNAL OF COMPARATIVE NEUROLOGY, 1992, 316 (02) : 238 - 250
  • [3] The foetal pig pineal gland is richly innervated by nerve fibres containing catecholamine-synthesizing enzymes, neuropeptide Y (NPY) and C-terminal flanking peptide of NPY, but it does not secrete melatonin
    Bulc, Michal
    Lewczuk, Bogdan
    Prusik, Magdalena
    Calka, Jaroslaw
    HISTOLOGY AND HISTOPATHOLOGY, 2013, 28 (05) : 633 - 646
  • [4] NEUROPEPTIDE TYROSINE (NPY) AND ITS C-TERMINAL FLANKING PEPTIDE (C-PON) IN THE DEVELOPING AND ADULT SPINAL-CORD OF A REPTILE
    MARTI, E
    BELLO, AR
    LANCHA, A
    BATISTA, MAP
    JOURNAL OF ANATOMY, 1990, 172 : 149 - 156
  • [5] Specific distribution pattern of nerve fibers containing catecholamine-synthesizing enzymes, neuropeptide Y (NPY) and C-terminal flanking peptide of NPY (CPON) in the pineal gland of the chinchilla (Chinchilla laniger) an immunohistochemical study
    Nowicki, M
    Wojtkiewicz, J
    Seremak, B
    Sulik, M
    Ostaszewski, J
    Lewczuk, B
    Majewski, M
    Przybylska-Gornowicz, B
    FOLIA HISTOCHEMICA ET CYTOBIOLOGICA, 2003, 41 (04) : 193 - 200
  • [6] Structure activity studies of mast cell activation and hypotension induced by neuropeptide Y (NPY), centrally truncated and C-terminal NPY analogues
    Cross, LJM
    BeckSickinger, AG
    Bienert, M
    Gaida, W
    Jung, WT
    Krause, E
    Ennis, M
    BRITISH JOURNAL OF PHARMACOLOGY, 1996, 117 (02) : 325 - 332
  • [7] C-terminal flanking peptide of neuropeptide Y in DRG following nerve compression
    Widerberg, A
    Kanje, M
    Dahlin, LB
    NEUROREPORT, 2001, 12 (15) : 3193 - 3196
  • [8] Quantitative Analysis of Neuropeptide Y (NPY) and C-Terminal Glycine-Extended NPY by Mass Spectrometry and Their Localization in the Developing and Sexual Adult Mouse Brains
    Yamagaki, Tohru
    Osugi, Tomohiro
    Shinmyo, Yohei
    Kawasaki, Hiroshi
    Satake, Honoo
    ACS CHEMICAL NEUROSCIENCE, 2025, 16 (04): : 588 - 594
  • [9] ANTAGONISM OF THE INHIBITORY-ACTION OF NEUROPEPTIDE-Y (NPY) IN GUINEA-PIG TRACHEA BY THE C-TERMINAL FRAGMENT NPY (2-36)
    BENCHEKROUN, MT
    STPIERRE, S
    FOURNIER, A
    CADIEUX, A
    BRITISH JOURNAL OF PHARMACOLOGY, 1993, 109 (04) : 902 - 904
  • [10] IMMUNOCYTOCHEMICAL LOCALIZATION OF NEUROPEPTIDE-Y AND ITS C-TERMINAL FLANKING PEPTIDE IN THE HUMAN HEART
    GULBENKIAN, S
    ANDRADE, NC
    WHARTON, J
    POLAK, JM
    MELO, JQ
    DAVIDFERREIRA, JF
    ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1990, 611 : 429 - 431