Relationship between post-traumatic stress disorder-like behavior and reduction of hippocampal 5-bromo-2′-deoxyuridine-positive cells after inescapable shock in rats

Akihito Kikuchi, Kunio Shimizu, Masashi Nibuya, Takeshi Hiramoto, Yasunari Kanda, Teppei Tanaka, Yasuhiro Watanabe, Yoshitomo Takahashi, Soichiro Nomura

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Aim: Inescapable shocks (IS) have been reported to reduce the number of 5-bromo-2′-deoxyuridine (BrdU)-positive cells in hippocampus. Antidepressants prevent this reduction, and the role of neurogenesis in depression is now suggested. It has been reported, however, that the number of BrdU-positive cells was not different between the rats that developed learned helplessness and those that did not. This suggests that reduction of neurogenesis does not constitute a primary etiology of depression. It has been previously shown that IS can cause various post-traumatic stress disorder (PTSD)-like behavioral changes in rats. The aim of the present was therefore to examined whether the reduction of BrdU-positive cells relates to any PTSD-like behavioral changes in this paradigm. Methods: Rats were given either inescapable foot-shocks (IS) or not shocked (non-S) treatment in a shuttle box on day 1 and received BrdU injections once daily during the first week after IS/non-S treatment. On day 14, rats treated with IS and non-S were given an avoidance/escape test in the shuttle box and dorsal hippocampal SGZ were analyzed by BrdU immunohistochemistry. Results: In accordance with previously reported results, IS loading resulted in fewer BrdU-positive cells in the hippocampal subgranular zone (SGZ). Furthermore, in the IS-treated group, the number of BrdU-positive cells in the hippocampal SGZ was negatively correlated at a significant level with several hyperactive behavioral parameters but not with hypoactive behavioral parameters. Earlier findings had indicated that chronic selective serotonin re-uptake inhibitor administration, which is known to increase hippocampal neurogenesis, restored the increase in hypervigilant/hyperarousal behavior but did not attenuate the increase in numbing/avoidance behavior. Conclusion: The regulatory mechanism responsible for the decreased proliferation and survival of cells in the hippocampus may be related to the pathogenic processes of hypervigilance/hyperarousal behaviors.

Original languageEnglish (US)
Pages (from-to)713-720
Number of pages8
JournalPsychiatry and Clinical Neurosciences
Volume62
Issue number6
DOIs
StatePublished - Dec 2008
Externally publishedYes

Fingerprint

Deoxyuridine
Bromodeoxyuridine
Post-Traumatic Stress Disorders
Shock
Neurogenesis
Hippocampus
Learned Helplessness
Depression
Avoidance Learning
Serotonin Uptake Inhibitors
Antidepressive Agents
Foot
Cell Survival
Anxiety
Immunohistochemistry
Cell Proliferation
Injections
Therapeutics

Keywords

  • Hippocampus
  • Neurogenesis
  • Post-traumatic stress disorder
  • Subgranular zone

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Psychiatry and Mental health
  • Neuroscience(all)

Cite this

Relationship between post-traumatic stress disorder-like behavior and reduction of hippocampal 5-bromo-2′-deoxyuridine-positive cells after inescapable shock in rats. / Kikuchi, Akihito; Shimizu, Kunio; Nibuya, Masashi; Hiramoto, Takeshi; Kanda, Yasunari; Tanaka, Teppei; Watanabe, Yasuhiro; Takahashi, Yoshitomo; Nomura, Soichiro.

In: Psychiatry and Clinical Neurosciences, Vol. 62, No. 6, 12.2008, p. 713-720.

Research output: Contribution to journalArticle

Kikuchi, Akihito ; Shimizu, Kunio ; Nibuya, Masashi ; Hiramoto, Takeshi ; Kanda, Yasunari ; Tanaka, Teppei ; Watanabe, Yasuhiro ; Takahashi, Yoshitomo ; Nomura, Soichiro. / Relationship between post-traumatic stress disorder-like behavior and reduction of hippocampal 5-bromo-2′-deoxyuridine-positive cells after inescapable shock in rats. In: Psychiatry and Clinical Neurosciences. 2008 ; Vol. 62, No. 6. pp. 713-720.
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abstract = "Aim: Inescapable shocks (IS) have been reported to reduce the number of 5-bromo-2′-deoxyuridine (BrdU)-positive cells in hippocampus. Antidepressants prevent this reduction, and the role of neurogenesis in depression is now suggested. It has been reported, however, that the number of BrdU-positive cells was not different between the rats that developed learned helplessness and those that did not. This suggests that reduction of neurogenesis does not constitute a primary etiology of depression. It has been previously shown that IS can cause various post-traumatic stress disorder (PTSD)-like behavioral changes in rats. The aim of the present was therefore to examined whether the reduction of BrdU-positive cells relates to any PTSD-like behavioral changes in this paradigm. Methods: Rats were given either inescapable foot-shocks (IS) or not shocked (non-S) treatment in a shuttle box on day 1 and received BrdU injections once daily during the first week after IS/non-S treatment. On day 14, rats treated with IS and non-S were given an avoidance/escape test in the shuttle box and dorsal hippocampal SGZ were analyzed by BrdU immunohistochemistry. Results: In accordance with previously reported results, IS loading resulted in fewer BrdU-positive cells in the hippocampal subgranular zone (SGZ). Furthermore, in the IS-treated group, the number of BrdU-positive cells in the hippocampal SGZ was negatively correlated at a significant level with several hyperactive behavioral parameters but not with hypoactive behavioral parameters. Earlier findings had indicated that chronic selective serotonin re-uptake inhibitor administration, which is known to increase hippocampal neurogenesis, restored the increase in hypervigilant/hyperarousal behavior but did not attenuate the increase in numbing/avoidance behavior. Conclusion: The regulatory mechanism responsible for the decreased proliferation and survival of cells in the hippocampus may be related to the pathogenic processes of hypervigilance/hyperarousal behaviors.",
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AU - Shimizu, Kunio

AU - Nibuya, Masashi

AU - Hiramoto, Takeshi

AU - Kanda, Yasunari

AU - Tanaka, Teppei

AU - Watanabe, Yasuhiro

AU - Takahashi, Yoshitomo

AU - Nomura, Soichiro

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N2 - Aim: Inescapable shocks (IS) have been reported to reduce the number of 5-bromo-2′-deoxyuridine (BrdU)-positive cells in hippocampus. Antidepressants prevent this reduction, and the role of neurogenesis in depression is now suggested. It has been reported, however, that the number of BrdU-positive cells was not different between the rats that developed learned helplessness and those that did not. This suggests that reduction of neurogenesis does not constitute a primary etiology of depression. It has been previously shown that IS can cause various post-traumatic stress disorder (PTSD)-like behavioral changes in rats. The aim of the present was therefore to examined whether the reduction of BrdU-positive cells relates to any PTSD-like behavioral changes in this paradigm. Methods: Rats were given either inescapable foot-shocks (IS) or not shocked (non-S) treatment in a shuttle box on day 1 and received BrdU injections once daily during the first week after IS/non-S treatment. On day 14, rats treated with IS and non-S were given an avoidance/escape test in the shuttle box and dorsal hippocampal SGZ were analyzed by BrdU immunohistochemistry. Results: In accordance with previously reported results, IS loading resulted in fewer BrdU-positive cells in the hippocampal subgranular zone (SGZ). Furthermore, in the IS-treated group, the number of BrdU-positive cells in the hippocampal SGZ was negatively correlated at a significant level with several hyperactive behavioral parameters but not with hypoactive behavioral parameters. Earlier findings had indicated that chronic selective serotonin re-uptake inhibitor administration, which is known to increase hippocampal neurogenesis, restored the increase in hypervigilant/hyperarousal behavior but did not attenuate the increase in numbing/avoidance behavior. Conclusion: The regulatory mechanism responsible for the decreased proliferation and survival of cells in the hippocampus may be related to the pathogenic processes of hypervigilance/hyperarousal behaviors.

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