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흰쥐에서 장기간 구속 스트레스 노출이 혈장 Corticosterone 농도와 시상하부 산화질소 합성효소 활성 변화에 미치는 급성 및 만성 효과

Effects of Chronic Repetitive Restraint Stress on Acute and Long-Term Changes in Plasma Corticosterone Levels and Hypothalamic Neuronal Nitric Oxide Synthase Activity in Rats

스트레스연구 2020년 28권 4호 p.285 ~ 291
박지혜, 임인환, Lee Seoul,
소속 상세정보
박지혜 ( Park Ji-Hye ) - Wonkwang University School of Medicine Department of Pharmacology
임인환 ( Lim In-Hwan ) - Wonkwang University School of Medicine Department of Neurology
 ( Lee Seoul ) - Wonkwang University School of Medicine Department of Pharmacology

Abstract

흰쥐를 구속 스트레스에 7일 동안 반복하여 노출시킨 후 체중 변화, 혈장 corticosterone 농도, 시상하부c-Fos, nNOS 활성, 청반 TH활성 및 탐색행동을 관찰하였다. 스트레스는 급성기 혈장 corticosterone 농도와 뇌실옆핵 c-fos, nNOS, 청반 TH 활성을 증가시키고 체중증가를 억제시켰다. 구속 스트레스를 중단하고 회복시킨 14일차에 측정한 만성기 corticosterone 농도와 nNOS활성 증가는 지속되어 있었다. 흰쥐에게 장기간 구속 스트레스는 혈장corticosterone과 시상하부 nNOS 활성을 증가시켰으며, 스트레스 중단 후에도 증가현상은 유지되었다. 이 결과는 스트레스에 의한 생리적 부적응으로 보이며, 시상하부 nNOS활성 증가가 원인으로 사료된다.

Background: Immobilization as restraint stress is recognized as a psychologically stressful event. The stress responses alter both neuroendocrine and neurochemistry in an acute and long-term manner. We investigated whether the effect of chronic repetitive restraint stress could elicit levels of corticosterone and related neurochemical alterations.

Methods: Nine-week-old Sprague-Dawley rats (the stressed group) were subjected to restraint stress in a hemi-cylindrical apparatus nocturnally in seven consecutive days. The handled control group was a sustained-controlled husbandry, and the stressed group was returned to the same home cage immediately after daily restraint sessions. On day 14, all subjects were sacrificed and neurochemical assessment was performed. Plasma corticosterone levels were measured on days 1, 7, and 14 following a 7-day recovery period. The activity of exploration was measured on day 5 of the stress session for 5 min to expose the novel open field. On day 14, tyrosine hydroxylase, c-fos, and NADPH-diaphorase immunohistochemistry was performed in the locus coeruleus and hypothalamic PVN (paraventricular nucleus) in the brain, respectively.

Results: The repetitive restraint stress elicits a retarded growth pattern and lowers locomotive activity at the acute phase. During the stressed session, higher levels of plasma corticosterone and nNOS (neuronal nitric oxide synthase) activity in the hypothalamus. Furthermore, the upregulated changes were prolonged seven days after the stress-free recovery period, chronically.

Conclusions: Chronic repetitive restraint stress may acutely alter neuroendocrine and behavioral changes via the hypothalamic-pituitary-adrenal axis, and its phenomenon is sustained as a physiological maladaptation, depending on neurochemical alterations related to hypothalamic nNOS activity.

키워드

스트레스반응; 스트레스대응축; 코르티코스테론; 신경성산화질소합성효소; 탐색행동
Stress response; Hypothalamic-pituitary-adrenal (HPA) axis; Corticosterone; nNOS; Exploration

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