Vulnerability in early life to changes in the rearing environment plays a crucial role in the aetiopathology of psychiatric disorders

Minae Niwa, Yurie Matsumoto, Akihiro Mouri, Norio Ozaki, Toshitaka Nabeshima

研究成果: Article

47 引用 (Scopus)

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Adverse events early in life, including maternal separation and social isolation, profoundly affect brain development and adult behaviour and may contribute to the occurrence of psychiatric disorders such as schizophrenia and mood disorders in genetically predisposed individuals. The molecular mechanisms underlying these environmentally induced developmental adaptations are unclear and best evaluated in animal paradigms with translational salience. In this study, we examined the effects in mice of maternal separation and/or social isolation for 6 h/d between postnatal days 15 and 21 on performance during adulthood in the open-field, social interaction, elevated plus-maze, forced swimming, Y-maze, novel object recognition, conditioned fear-learning, prepulse inhibition, and locomotor activity tests, to investigate whether this animal model could show the phenotypes for schizophrenia and mood disorders. The stress of maternal separation and isolation led to adult behavioural deficits, activation of the hypothalamic-pituitary-adrenal axis, and decreases in the levels of norepinephrine and dopamine in the frontal cortex and metabolites of dopamine and serotonin in the amygdala, showing the involvement of endocrine and neuronal risk in behavioural deficits. The results suggest that the frontal cortex and amygdala undergo structural remodelling induced by the stress of maternal separation and isolation, which alters behavioural and physiological responses in adulthood, including anxiety, memory and other cognitive processes. Further, social isolation enhanced the behavioural dysfunctions induced by maternal separation. These findings indicate that maternal separation and social isolation early in life can lead to long-lasting abnormal behaviour and pathophysiological impairments including schizophrenia and mood disorders.

元の言語English
ページ(範囲)459-477
ページ数19
ジャーナルInternational Journal of Neuropsychopharmacology
14
発行部数4
DOI
出版物ステータスPublished - 01-05-2011
外部発表Yes

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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