title: Neonatal isolation changes the expression of IGF-IR and IGFBP-2 in the hippocampus in response to adulthood restraint stress.
abstract: Early adverse experiences are thought to contribute to the development of stress vulnerability, and to increase the onset of stress-related psychiatric disorders in stressful environments in adulthood. One plausible molecular mechanism of stress vulnerability is the modulation of neurotrophic factor signal transduction in the hippocampus by early adversity. In the present study we investigated the influence of neonatal isolation (NI) with or without adulthood single restraint stress (SRS) on the expression of several growth factor-related genes in the rat hippocampus using a cDNA microarray, real-time quantitative PCR, and Western blot. We found that hippocampal insulin-like growth factor-I receptor (IGF-IR) mRNA levels and immunoreactivity, and IGF binding protein-2 (IGFBP-2) mRNA levels were significantly lower in response to SRS in NI rats compared with rats without NI. Immunohistochemical analyses revealed that hippocampal IGF-IR immunoreactivity in the CA1 and CA3 pyramidal cell layers, and in the dentate gyrus granule cell layer of NI rats subjected to SRS was significantly lower compared with rats subjected to SRS. In addition, the hippocampal levels of IGF-IR mRNA were significantly lower in adult rats subjected to NI. These findings indicate that NI down-regulates IGF signal transduction under basal and stressful conditions in later life. Since the activation of IGF signalling plays a role in the development and neuroprotection of the central nervous system, the down-regulation of IGF signal transduction induced by NI may be, at least in part, involved in the development of adulthood stress vulnerability, which in turn precipitates the onset of depression.
authors.affiliation: Department of Psychiatry and Neurosciences, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Erabi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Morinobu
authors.forename: Ki-ichiro
authors.initials: K
authors.lastname: Kawano
authors.forename: Seiichi
authors.initials: S
authors.lastname: Tsuji
authors.forename: Shigeto
authors.initials: S
authors.lastname: Yamawaki
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D015153:Blotting, Western; D003345:Corticosterone / Q000097:blood; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis*; D012149:Restraint, Physical; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012934:Social Isolation / Q000523:psychology*; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology
chemical_list: D000199:Actins; D018076:DNA, Complementary; D018971:Insulin-Like Growth Factor Binding Protein 2; D012333:RNA, Messenger; D017526:Receptor, IGF Type 1; D003345:Corticosterone