TY - JOUR
T1 - Generation and characterization of conditional heparin-binding EGF-like growth factor knockout mice
AU - Oyagi, Atsushi
AU - Oida, Yasuhisa
AU - Kakefuda, Kenichi
AU - Shimazawa, Masamitsu
AU - Shioda, Norifumi
AU - Moriguchi, Shigeki
AU - Kitaichi, Kiyoyuki
AU - Nanba, Daisuke
AU - Yamaguchi, Kazumasa
AU - Furuta, Yasuhide
AU - Fukunaga, Kohji
AU - Higashiyama, Shigeki
AU - Hara, Hideaki
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2009/10/14
Y1 - 2009/10/14
N2 - Recently, neurotrophic factors and cytokines have been shown to be associated in psychiatric disorders, such as schizophrenia, bipolar disorder, and depression. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family, serves as a neurotrophic molecular and plays a significant role in the brain. We generated mice in which HB-EGF activity is disrupted specifically in the ventral forebrain. These knockout mice showed (a) behavioral abnormalities similar to those described in psychiatric disorders, which were ameliorated by typical or atypical antipsychotics, (b) altered dopamine and serotonin levels in the brain, (c) decreases in spine density in neurons of the prefrontal cortex, (d) reductions in the protein levels of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor and post-synaptic protein-95 (PSD-95), (e) decreases in the EGF receptor, and in the calcium/calmodulin-dependent protein kinase II (CaMK II) signal cascade. These results suggest the alterations affecting HB-EGF signaling could comprise a contributing factor in psychiatric disorder.
AB - Recently, neurotrophic factors and cytokines have been shown to be associated in psychiatric disorders, such as schizophrenia, bipolar disorder, and depression. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family, serves as a neurotrophic molecular and plays a significant role in the brain. We generated mice in which HB-EGF activity is disrupted specifically in the ventral forebrain. These knockout mice showed (a) behavioral abnormalities similar to those described in psychiatric disorders, which were ameliorated by typical or atypical antipsychotics, (b) altered dopamine and serotonin levels in the brain, (c) decreases in spine density in neurons of the prefrontal cortex, (d) reductions in the protein levels of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor and post-synaptic protein-95 (PSD-95), (e) decreases in the EGF receptor, and in the calcium/calmodulin-dependent protein kinase II (CaMK II) signal cascade. These results suggest the alterations affecting HB-EGF signaling could comprise a contributing factor in psychiatric disorder.
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U2 - 10.1371/journal.pone.0007461
DO - 10.1371/journal.pone.0007461
M3 - Article
C2 - 19829704
AN - SCOPUS:70449338128
VL - 4
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 10
M1 - e7461
ER -