Schmidt Mathias V, Oitzl Melly S, Levine Seymour, de Kloet E Ronald
Leiden/Amsterdam Center for Drug Research/Leiden University Medical Center, Division of Medical Pharmacology, Gorlaeus Laboratories, PO Box 9502, 2300 RA Leiden, The Netherlands.
Brain Res Dev Brain Res. 2002 Nov 15;139(1):39-49. doi: 10.1016/s0165-3806(02)00519-9.
In this study we describe in 9- and 18-day-old CD1 mice (i) the basal and stress-induced activity of markers of the HPA system in blood, brain and pituitary, (ii) the effects of a 24-h maternal deprivation and (iii) the influence of anogenital stimulation (stroking) in deprived pups on these markers. We found low basal concentrations of ACTH and corticosterone at postnatal day (pnd) 9 and no or little response to a mild stressor at this age, confirming the existence of a SHRP in mice. At pnd 18 the mice displayed an adult-like ACTH and corticosterone response following a mild stressor. Maternal deprivation resulted in enhanced basal and stress levels of corticosterone at both ages. Interestingly, basal ACTH levels were elevated following maternal deprivation at pnd 9. At pnd 18 maternal deprivation resulted in a blunted ACTH response. Maternal deprivation resulted in a down-regulation of GR, MR, CRH and POMC transcript in the brain. However, maternally deprived 18-day-old pups displayed increased levels of CRH and POMC transcript, while GR and MR mRNA was also down-regulated. Anogenital stroking could reverse maternal deprivation effects on ACTH and MR mRNA, but not CRH mRNA. We conclude that (i) at the two measured time points the HPA axis develops similar in mice as in rats, (ii) maternal deprivation has pronounced effects in mice, which are similar to that found in the rat and (iii) there are a number of significant differences, which mainly concern the central CRH-ACTH components of the axis.
在本研究中,我们描述了9日龄和18日龄的CD1小鼠:(i)血液、大脑和垂体中HPA系统标志物的基础活性和应激诱导活性;(ii)24小时母婴分离的影响;(iii)对剥夺幼崽进行肛门生殖器刺激(抚摸)对这些标志物的影响。我们发现,出生后第9天(pnd9)促肾上腺皮质激素(ACTH)和皮质酮的基础浓度较低,且该年龄段对轻度应激源无反应或反应很小,这证实了小鼠中存在应激低反应期(SHRP)。在pnd18时,小鼠在轻度应激源刺激后表现出类似成年小鼠的ACTH和皮质酮反应。母婴分离导致两个年龄段的皮质酮基础水平和应激水平均升高。有趣的是,pnd9时母婴分离后基础ACTH水平升高。在pnd18时,母婴分离导致ACTH反应减弱。母婴分离导致大脑中糖皮质激素受体(GR)、盐皮质激素受体(MR)、促肾上腺皮质激素释放激素(CRH)和阿黑皮素原(POMC)转录本下调。然而,母婴分离的18日龄幼崽CRH和POMC转录本水平升高,而GR和MR mRNA也下调。肛门生殖器抚摸可逆转母婴分离对ACTH和MR mRNA的影响,但不能逆转对CRH mRNA的影响。我们得出结论:(i)在两个测量时间点,小鼠HPA轴的发育与大鼠相似;(ii)母婴分离对小鼠有显著影响,与在大鼠中发现的类似;(iii)存在一些显著差异,主要涉及该轴的中枢CRH-ACTH成分。