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Study on Emotional Neuroplasticity in the Pathophysiology of Affective Disorders

Research Project

Project/Area Number 14390037
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 広領域
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

YAMAWAKI Shigeto  Hiroshima University, Graduate School of Biomedical Science, Professor, 大学院・医歯薬学総合研究科, 教授 (40230601)

Co-Investigator(Kenkyū-buntansha) MORINOBU Shigeru  Hiroshima University, Graduate School of Biomedical Science, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (30191042)
OKAMOTO Yasumasa  Hiroshima University, Graduate School of Biomedical Science, Assistant Professor, 大学院・医歯薬学総合研究科, 講師 (70314763)
加賀屋 有行 (加賀谷 有行)  広島国際大学, 医療福祉学部, 教授 (60274065)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 2004: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥5,800,000 (Direct Cost: ¥5,800,000)
KeywordsMood Disorders / Depression / PTSD / Neuroplasticity / Maternal Deprivation / Stress Vulnerability / hippocampus / Sensory Gating System / 摂食障害 / 母子分離動物モデル / 前頭前野 / 双極性障害神経可塑性神経可塑性 / 動物モデル / 双極性障害 / 神経栄養因子
Research Abstract

Since emotional neuroplasticity is reported to be associated with the pathogenesis of mood disorders, we examined the mechanism of neuroplasticity in an animal model of stress-related disorders, and patients with depression.
1)Stress-induced changes in neuroplasticity
Hippocampal neuroplasticity regulated by neurotrophic factors, plays a role in the development of emotional memory. We examined whether neonatal isolation (NI) or NI with a single restraint stress (SRS) changed the levels of several neurotrophioc factors in the adult rat hippocampus. Whereas NI had no changes in the levels of NGF,BDNF,GDNF,NT-3,IGFR1,IGFR2, or IGFBP2 mRNA, NI + SRS significantly downregulated the levels of GDNF,NGF,IGFR1, and IGFBP2 mRNA. These findings suggest that early adverse experience may affect the development of hippocampal neuroplasticity mediated by neurotrophic factors.
2)Changes in fear and hippocampal gene expression in rats subjected to a single prolonged stress (SPS), an animal model of PTSD
To … More elucidate the molecular pathophysiology of PTSD, we assessed contextual freezing (CF) after fear conditioning and examined the change in hippocampal gene expression involved in the alteration of CF in rats subjected to SPS. The SPS rats showed a significant increase in CF, and cDNA microarray analysis revealed a significant increase in the levels of vesicle associated membrane protein 2(VAMP2). These findings suggest that VAMP2 may be involved in the enhanced CF in SPS rats.
3)Emotional neuroplasticity in patients with depression
To clear the difference for emotional neuroplasticity between depressive patients and healthy controls, we have analyzed the sensory gating system used by Magnetoencepharography(MEG). As a result, depressed patients had the different modulation in sensory gating system by emotional neuroplasticity. These results suggest that the broken sensory gating system in depressed patients might be correlated with vulnerability for stress as the risk for affective disorders. Less

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (53 results)

All 2005 2004 Other

All Journal Article (28 results) Publications (25 results)

  • [Journal Article] Visual emotional stimuli modulate auditory sensory gating studied by magnetic P50 suppression.2005

    • Author(s)
      Yamashita, H.
    • Journal Title

      European Archives of Psychiatry and Clinical Neuroscience

      Pages: 99-103

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Reduced activation of posterior cingulate cortex during imagery in subjects with high degrees of alexithymia : an fMRI study.2005

    • Author(s)
      Mantani, T.
    • Journal Title

      Biological Psychiatry

      Pages: 982-990

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Gender differences in brain activity generated by unpleasant word stimuli concerning body image : an fMRI study.2005

    • Author(s)
      Shirao, N., Okamoto, Y., Mantani, T., Okamoto, Y., Yamawaki, S.
    • Journal Title

      The British Jornal of Psychiatry 186

      Pages: 48-53

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Visual emotional stimuli modulation of auditory sensory gating studied by magnetic P50 suppression.2005

    • Author(s)
      Yamashita, H., Okamoto, Y., Morinobu, S., Yamawaki, S., Kahkonen, S.
    • Journal Title

      Eur Arch Psychiatry Clinical Neurosci. 255

      Pages: 99-103

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Reduced activation of posterior cingulate cortex during imagery in subjects with high degrees of alexithymia : an fMRI study.2005

    • Author(s)
      Mantani, T., Okamoto, Y., Shirao, N., Okada, G., Yamawaki, S.
    • Journal Title

      Biological Psychiatry 57

      Pages: 982-990

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Influence of immobilization stress on the levels of CaMKII and phospho-CaMKII in the rat hippocampus.2004

    • Author(s)
      Suenaga, T.
    • Journal Title

      International Journal of Neuropsychopharmacology 7

      Pages: 299-309

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Reduction in levels of amphiphysin 1 mRNA in the hippocampus of aged rats subjected to repeated variable stress.2004

    • Author(s)
      Sawada, T.
    • Journal Title

      Neuroscience 126

      Pages: 461-466

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Effect of neonatal isolation on the noradrenergic transduction system in the rat hippocampal slice.2004

    • Author(s)
      Kusaka, K.
    • Journal Title

      Synapse 54

      Pages: 223-232

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] β-estradiol, dehydroepiandrosterone, and dehydroepiandrosterone sulfate protect against N-Methyl-D-aspartate-induced neurotoxicity in rat hippocampal neurons by different mechanisms.2004

    • Author(s)
      Kurata, K.
    • Journal Title

      The Journal of Pharmacology and Experimental Therapeutics 311

      Pages: 237-245

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Lithium and protein phosphatases : apoptosis or neurogenesis?2004

    • Author(s)
      Morinobu, S.
    • Journal Title

      Clinical Neuroscience Research 4

      Pages: 263-269

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Negative correlation between right prefrontal activity during response inhibition and impulsiveness : a fMRI study.2004

    • Author(s)
      Asahi, S.
    • Journal Title

      European Archives of Psychiatry and Clinical Neuroscience 254

      Pages: 245-251

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Prediction of immediate and future rewards differentially recruits cortico-basal ganglia loops.2004

    • Author(s)
      Tanaka, SC.
    • Journal Title

      Nature Neuroscience 7

      Pages: 887-893

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Effects of changing from typical to atypical antipsychotic drugs on subjective sleep quality in patients with schizophrenia in a Japanese population.2004

    • Author(s)
      Yamashita, H.
    • Journal Title

      The Journal of Clinical Psychiatry 65

      Pages: 1525-1530

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Gender differences in brain activity toward unpleasant word stimuli concerning body image : an fMRI study.2004

    • Author(s)
      Shirao, N.
    • Journal Title

      The British Journal of Psychiatry 186

      Pages: 48-53

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Influence of immobilization stress on the levels of CaMKII and phospho-CaMKII in the rat hippocampus.2004

    • Author(s)
      Suenaga, T., Morinogu, S., Kawano, K., Sawada, T., Yamawaki, S.
    • Journal Title

      International Journal of Neuropsychopharmacology 7

      Pages: 299-309

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Reduction in levels of amphiphysin 1 mRNA in the hippocampus of aged rats subjected to repeated variable stress.2004

    • Author(s)
      Sawada, T., Morinobu, S., Tsuji, S., Kawano, K., Watanabe, T., Suenaga, T., Takahashi, T., Yamawaki, S., Nishida, A.
    • Journal Title

      Neuroscience 126

      Pages: 461-466

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effect of neonatal isolation on the noradrenergic transduction system in the rat hippocampal slice.2004

    • Author(s)
      Kusaka, K., Morinobu, S., Kawano, K., Yamawaki, S.
    • Journal Title

      Synapse 54

      Pages: 223-232

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] β-estradiol, dehydroepiandrosterone, and dehydroepiandrosterone sulfate protect against N-Methyl-D-aspartate-induced neurotoxicity in rat hippocampal neurons by different mechanisms.2004

    • Author(s)
      Kurata, K., Takebayashi, M., Morinobu, S., Yamawaki, S.
    • Journal Title

      The Journal of Pharmacology and Experimental Therapeutics. 311

      Pages: 237-245

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Lithium and protein phosphatases : apoptosis or neurogenesis?2004

    • Author(s)
      Morinobu, S., Kawano, K., Yamawaki, S.
    • Journal Title

      Clinical Neuroscience Research 4

      Pages: 263-269

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Negative correlation between right prefrontal activity during response inhibition and impulsiveness : A fMRI study.2004

    • Author(s)
      Asahi, S., Okamoro, Y., Okada, G., Yamawaki, S., Yokota, N.
    • Journal Title

      European Archives of Psychiatry and Clinical Neuroscience 254

      Pages: 245-251

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Prediction of immediate and future rewards differentially recruits cortico-basal ganglia loops.2004

    • Author(s)
      Tanaka, SC., Doya, K., Okada, G., Ueda, K., Okamoto, Y., Yamawaki, S.
    • Journal Title

      Nature Neuroscience 7

      Pages: 887-893

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of changing from typical to atypical antipsychotic drugs on subjective sleep quality in patients with schizophrenia in a Japanese population.2004

    • Author(s)
      Yamashita, H., Mori, K., Nagao, M., Okamoto, Y., Morinobu, S., Yamawaki, S.
    • Journal Title

      The Journal of Clinical Psychiatry 65

      Pages: 1525-1530

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Gender differences in brain activity toward unpleasant word stimuli concerning body image : an fMRI study.2004

    • Author(s)
      Shirao, N.
    • Journal Title

      The British Jornal of Psychiatry 186

      Pages: 48-53

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Gender differences in brain activity toward unpleasant linguistic stimuli concerning interpersonal relationships : an fMRI study.

    • Author(s)
      Shirao, N.
    • Journal Title

      European Archives of Psychiatry and Clinical Neuroscience (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Gender differences in brain activity toward unpleasant linguistic stimuli concerning interpersonal relationships : an fMRI study.

    • Author(s)
      Shirao, N., Okamoto, Y., Okada, G., Ueda, K., Yamawaki, S.
    • Journal Title

      European Archives of Psychiatry and Clinical Neuroscience (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Visual emotional stimuli modulate auditory sensory gating studied by magnetic P50 suppression.

    • Author(s)
      Yamashita, H.
    • Journal Title

      European Archives of Psychiatry and Clinical Neuroscience (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Gender differences in brain activity toward unpleasant linguistic stimuli concerning interpersonal relationships : an fMRI study.

    • Author(s)
      Shirao, N.
    • Journal Title

      European Archives of Psychiatry and Clinical Neuroscience (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Reduced activation of posterior cingulate cortex during imagery in subjects with high degrees of alexithymia : an fMRI study.

    • Author(s)
      Mantani, T.
    • Journal Title

      Biological Psychiatry (in press)

    • Related Report
      2004 Annual Research Report
  • [Publications] Okada, G.: "Attenuated left prefrontal activation during a verbal fluency task in patients with depression"Neuropsychobiology. 47. 21-26 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Inoue, S.: "Factors related to patient's mental adjustment to breast cancer : patient characteristics and family functioning"Supportive Care in Cancer. 11. 178-184 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ueda, K.: "Brain activity during expectancy of emotional stimuli : an fMRI study"Neuroreport. 14. 51-55 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsuji, S.: "Lithium, but not valproate, induces the serine/threonine phosphatase activity of protein phosphatase 2A in the rat brain, without affecting its expression"Journal of Neural Transmission. 110. 413-425 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Katagiri, H.: "Effect of repeated treatment with lamotrigine on locomotor activity and on DOI-elicited wet dog shakes in rats"Biogenic Amines. 17. 149-159 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Matsuoka, Y.: "A volumetric study of amygdala in cancer survivors with intrusive recollections"Biological Psychiatry. 54. 736-743 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Morinobu, S.: "Influence of immobilization on stress on the expression and phosphatase activity of protein phosphatase 2A in the rat brain"Biological Psychiatry. 54. 1060-1066 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kagaya, A.: "Mood disturbance and neurosteroids in women with breast cancer"Stress and Health. 19. 227-231 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shirao, N.: "Temporomesial activation in young females assosiated with unpleasant words concerning body image"Neuropsychobiology. 48. 136-142 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tanaka, S.: "Different cortico-basal ganglia loops specialize in reward prediction on different time scales"Neural Information Processing Systems. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Asahi, S.: "Negative correlation between right prefrontal activity during response inhibition and impulsiveness : A fMRI study"European Archives of Psychiatry and Clinical Neuroscience. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Suenaga, T.: "Influence of immobilization stress on the levels of CaMKII and phospho-CaMKII in the rat hippocampus"International Journal of Neuropsychopharmacology. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamashita, H.: "Cognitive dysfunction in recovered depressive patients with silent cerebral infarction"Neuropsychobiology. 45. 12-18 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tamura, T.: "The effects of antidepressant drug treatments on activator protein-1 binding activity in the rat brain"Progress in Neuro-Psychopharmacology & Biological Psychiatry. 26. 375-381 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mori, K.: "Effects of anticholinergic drug withdrawal on memory, regional cerebral blood flow and extrapyramidal side effects in schizophrenic patients"Pharmacopsychiatry. 35. 6-11 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamashita, H.: "Effect of risperidone on sleep in schizophrenia : a comparison with haloperidol"Psychiatry Research. 109. 137-142 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsuji, S.: "Meige syndrome with apraxia of lid opening after the discontinuation of sulpiride treatment"Pharmacopsychiatry. 35. 155-156 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tanaka, K.: "Imipramine, but not lithium, induces the serine / threonine phosphatase activity of calcineurin without affecting its mRNA expression in the rat brain"Psychopharmacology. 162. 339-344 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Asahi, S.: "A case of myclonus, resembling epileptic seizure, induced by short-term sulpiride treatment"International Journal of Psychiatry in Clinical Practice. 6. 215-216 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Uchitomi, Y.: "Lack of association between suicidal ideation and enhanced platelet 5-HT2A receptor-Mediated calcium mobilization in cancer patients with depression"Biological Psychiatry. 52. 1159-1165 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakae, S.: "Serotonin-2A receptor and the receptor-mediated signaling systems in rats : possible inplication for pathophysiology of mood disorders"Current Topics in Neurochemistry. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Okada, G.: "Attenuated left prefrontal activation during a verbal fluency task in patients with depression"Neuropsychobiology. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsuji, S.: "Lithium, but not valproate, induces the serine / threonine phosphatase activity of protein phoshatase 2A in the rat brain, without affecting its expression"Journal of Neural Transmission. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Morinobu, S.: "Catecholamine Research : From Molecular Insights to Clinical Medicine"Kluwer Academic Plenum Publishers. 3 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujikawa, T.: "Recent Advances in the Research of Affective Disorder in Japan"Elsevier Science. 7 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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