Neonatal isolation changes the expression of IGF-IR and IGFBP-2 in the hippocampus in response to adulthood restraint stress.
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.
Erabi
Kaori
K
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.
Morinobu
Shigeru
S
Kawano
Ki-ichiro
K
Tsuji
Seiichi
S
Yamawaki
Shigeto
S
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
D000199:Actins; D018076:DNA, Complementary; D018971:Insulin-Like Growth Factor Binding Protein 2; D012333:RNA, Messenger; D017526:Receptor, IGF Type 1; D003345:Corticosterone