Chronic restraint stress impairs neurogenesis and hippocampus-dependent fear memory in mice

Possible involvement of a brain-specific transcription factor Npas4

Jaesuk Yun, Hiroyuki Koike, Daisuke Ibi, Erika Toth, Hiroyuki Mizoguchi, Atsumi Nitta, Masanori Yoneyama, Kiyokazu Ogita, Yukio Yoneda, Toshitaka Nabeshima, Taku Nagai, Kiyofumi Yamada

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Neurogenesis in the hippocampus occurs throughout life in a wide range of species and could be associated with hippocampus-dependent learning and memory. Stress is well established to seriously perturb physiological/psychological homeostasis and affect hippocampal function. In the present study, to investigate the effect of chronic restraint stress in early life on hippocampal neurogenesis and hippocampus-dependent memory, 3-week-old mice were subjected to restraint stress 6 days a week for 4 weeks. The chronic restraint stress significantly decreased the hippocampal volume by 6.3% and impaired hippocampal neurogenesis as indicated by the reduced number of Ki67-, 5-bromo-2′- deoxyuridine- and doublecortin-positive cells in the dentate gyrus. The chronic restraint stress severely impaired hippocampus-dependent contextual fear memory without affecting hippocampus-independent fear memory. The expression level of brain-specific transcription factor neuronal PAS domain protein 4 (Npas4) mRNA in the hippocampus was down-regulated by the restraint stress or by acute corticosterone treatment. Npas4 immunoreactivity was detected in progenitors, immature and mature neurons of the dentate gyrus in control and stressed mice. Our findings suggest that the chronic restraint stress decreases hippocampal neurogenesis, leading to an impairment of hippocampus-dependent fear memory in mice. Corticosterone-induced down-regulation of Npas4 expression may play a role in stress-induced impairment of hippocampal function.

Original languageEnglish
Pages (from-to)1840-1851
Number of pages12
JournalJournal of Neurochemistry
Volume114
Issue number6
DOIs
Publication statusPublished - 01-01-2010
Externally publishedYes

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Neurogenesis
Fear
Hippocampus
Brain
Transcription Factors
Data storage equipment
Dentate Gyrus
Corticosterone
Bromodeoxyuridine
Homeostasis
Neurons
Down-Regulation
Learning
Psychology
Cells
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Yun, Jaesuk ; Koike, Hiroyuki ; Ibi, Daisuke ; Toth, Erika ; Mizoguchi, Hiroyuki ; Nitta, Atsumi ; Yoneyama, Masanori ; Ogita, Kiyokazu ; Yoneda, Yukio ; Nabeshima, Toshitaka ; Nagai, Taku ; Yamada, Kiyofumi. / Chronic restraint stress impairs neurogenesis and hippocampus-dependent fear memory in mice : Possible involvement of a brain-specific transcription factor Npas4. In: Journal of Neurochemistry. 2010 ; Vol. 114, No. 6. pp. 1840-1851.
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Chronic restraint stress impairs neurogenesis and hippocampus-dependent fear memory in mice : Possible involvement of a brain-specific transcription factor Npas4. / Yun, Jaesuk; Koike, Hiroyuki; Ibi, Daisuke; Toth, Erika; Mizoguchi, Hiroyuki; Nitta, Atsumi; Yoneyama, Masanori; Ogita, Kiyokazu; Yoneda, Yukio; Nabeshima, Toshitaka; Nagai, Taku; Yamada, Kiyofumi.

In: Journal of Neurochemistry, Vol. 114, No. 6, 01.01.2010, p. 1840-1851.

Research output: Contribution to journalArticle

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AU - Yun, Jaesuk

AU - Koike, Hiroyuki

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AU - Toth, Erika

AU - Mizoguchi, Hiroyuki

AU - Nitta, Atsumi

AU - Yoneyama, Masanori

AU - Ogita, Kiyokazu

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AU - Nabeshima, Toshitaka

AU - Nagai, Taku

AU - Yamada, Kiyofumi

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