title: HCNP precursor protein transgenic mice display a depressive-like phenotype in old age.
abstract: We have previously reported a novel peptide, hippocampal cholinergic neurostimulating peptide (HCNP), which induces acetylcholine synthesis by increasing the amount of cholineacetyltransferase (ChAT) in medial septal nuclei. The HCNP precursor protein, composed of 186 amino acids, is an inhibitory factor of the c-Raf/ MEK cascade and may be involved in the development of the fetal rat brain via the inhibition of Erk phosphorylation. To clarify the involvement of HCNP in hippocampal cholinergic circuitry, we previously generated HCNP precursor protein (HCNP-pp) transgenic mice using the promoter of the alpha subunit of Ca(2+) calmodulin-dependent protein kinase II (CaMKIIalpha). These mice showed increased levels of ChAT in medial septal nuclei. Here, we investigated the behavioral phenotype of these mice, such as locomotor activity, mood and working/spatial memory. We demonstrate that HCNP-pp transgenic mice show a depressive-like phenotype at 30 weeks of age, but not at 12 weeks of age. We suggest that either HCNP and/or HCNP precursor protein may evoke the depressive-like phenotype via cholinergic hyperactivity from early neonatal life and/or inhibition of phosphorylated Erk in the neonatal hippocampus.
authors.affiliation: Department of Neurology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-ku, Nagoya 467-8601, Japan. norim@med.nagoya-cu.ac.jp
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Matsukawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Furuya
authors.forename: Hiroo
authors.initials: H
authors.lastname: Ogura
authors.forename: Kosei
authors.initials: K
authors.lastname: Ojika
mesh_terms: D000367:Age Factors; D000375:Aging; D000818:Animals; D001522:Behavior, Animal; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003863:Depression / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D019417:Hindlimb Suspension / Q000523:psychology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009433:Neural Inhibition / Q000235:genetics; D009479:Neuropeptides / Q000378:metabolism; D010641:Phenotype; D049488:Phosphatidylethanolamine Binding Protein / Q000235:genetics*; D013550:Swimming / Q000523:psychology
chemical_list: D009479:Neuropeptides; D049488:Phosphatidylethanolamine Binding Protein; C075274:hippocampal cholinergic neurostimulating peptide; D002795:Choline O-Acetyltransferase