The maternal deprivation animal model revisited

Early life stress, in the form of MD (24 h at pnd 9), interferes with brain developmental trajectories modifying both behavioral and neurobiochemical parameters. MD has been reported to enhance neuroendocrine responses to stress, to affect emotional behavior and to impair cognitive function. More recently, changes in body weight gain, metabolic parameters and immunological responding have also been described. Present data give support to the fact that neuronal degeneration and/or astrocyte proliferation are present in specific brain regions, mainly hippocampus, prefrontal cortex and hypothalamus, which are particularly vulnerable to the effects of neonatal stress. The MD animal model arises as a valuable tool for the investigation of the brain processes occurring at the narrow time window comprised between pnd 9 and 10 that are critical for the establishment of brain circuitries critical for the regulation of behavior, metabolism and energy homeostasis. In the present review we will discuss three possible mechanisms that might be crucial for the effects of MD, namely, the rapid increase in glucocorticoids, the lack of the neonatal leptin surge, and the enhanced endocannabinoid signaling during the specific critical period of MD. A better understanding of the mechanisms underlying the detrimental consequences of MD is a concern for public health and may provide new insights into mental health prevention strategies and into novel therapeutic approaches in neuropsychiatry.     

Effects of different adrenergic blockades on the stress resistance of Wistar rats

The coordinated responses of the sympathoadreno-medullary (SAM) system and hypothalamic-pituitary-adrenal (HPA) axis could improve the organism's capacity to cope with stress, but its underlying mechanism is still unclear. In the present study, 32 Wistar rats were employed and divided into four groups: control, CUMS, PROP and PRAZ. After the chronic unpredicted mild stress (CUMS) model was built in the latter three groups, all animals were exposed to inescapable footshock. We found that α₁-adrenoceptor antagonist prazosin (PRAZ) administration could improve behavior changes, reduce the cellular impairment in brain and inhibit the hyperfunction of HPA axis induced by CUMS exposure. Moreover, it decreased the heat shock protein 70 and inducible nitric oxide synthase expression in different brain areas as subsequently exposed to acute stress. In conclusion, α1-adrenoceptor may play a major role in regulating the coordinated responses between two physiological axes and improve the stress resistance.     

Endogenous Glucocorticoids Participate in Retinal Degeneration During Continuous Illumination

Continuous illumination (CI) induces an oxidative stress of the retina which is involved in light-induced retinal degeneration (LIRD). As the increase of glucocorticoids (GC) could also collaborate in the damage, adrenalectomized (ADX) and sham-operated rats (control, CTL) were submitted to CI, and their eyes were studied at light and electron microscopic levels. After CI, ADX retinas were significantly thicker than CTL retinas. Retinal alterations appeared earlier and were severer in CTL than in ADX retinas. Corticosterone levels increased gradually in the sera of CTL rats along CI. These results suggest that adrenalectomy attenuates LIRD, supporting the hypothesis.     

亚低温对脑心综合征大鼠血清皮质酮变化的影响及意义

目的探讨亚低温对急性脑梗死(ACI)并发脑心综合征(CCS)大鼠血清皮质酮(CORT)变化的影响及意义。方法将实验大鼠随机分为亚低温组、常温组及假手术组,亚低温组及常温组采用线栓法栓塞大鼠右侧大脑中动脉,术后连续监测标准Ⅱ导联心电图2h,统计各组脑心综合征的发病率,检测术后2h、24h、48h血清皮质酮的水平。结果亚低温组较常温组脑心综合征发病率低(P0.05);常温组及亚低温组各时间点皮质酮水平均较假手术组增高,差异有统计学意义(P0.05),常温组各时间点皮质酮水平均较亚低温组高,但只在2h点差别有统计学意义(P0.05)。结论亚低温可能通过稳定应激激素的水平降低急性脑梗死大鼠并发脑心综合征的发病率。     

Effect of Beta-Asarone on Impairment of Spatial Working Memory and Apoptosis in the Hippocampus of Rats Exposed to Chronic Corticosterone Administration

β-asarone (BAS) is an active component of Acori graminei rhizoma, a traditional medicine used clinically in treating dementia and chronic stress in Korea. However, the cognitive effects of BAS and its mechanism of action have remained elusive. The purpose of this study was to examine whether BAS improved spatial cognitive impairment induced in rats following chronic corticosterone (CORT) administration. CORT administration (40 mg/kg, i.p., 21 days) resulted in cognitive impairment in the avoidance conditioning test (AAT) and the Morris water maze (MWM) test that was reversed by BAS (200 mg/kg, i.p). Additionally, as assessed by immunohistochemistry and RT-PCR analysis, the administration of BAS significantly alleviated memory-associated decreases in the expression levels of brain-derived neurotrophic factor (BDNF) and cAMP-response element-binding protein (CREB) proteins and mRNAs in the hippocampus. Also, BAS administration significantly restored the expression of Bax and Bcl-2 mRNAs in the hippocampus. Thus, BAS may be an effective therapeutic for learning and memory disturbances, and its neuroprotective effect was mediated, in part, by normalizing the CORT response, resulting in regulation of BDNF and CREB functions and anti-apoptosis in rats.     

Amphibian immunity–stress,disease, and climate change

Like all other vertebrate groups, amphibian responses to the environment are mediated through the brain (hypothalamic)-pituitary-adrenal/interrenal (HPA/I) axis and the sympathetic nervous system. Amphibians are facing historically unprecedented environmental stress due to climate change that will involve unpredictable temperature and rainfall regimes and possible nutritional deficits due to extremes of temperature and drought. At the same time, amphibians in all parts of the world are experiencing unprecedented declines due to the emerging diseases, chytridiomycosis (caused by Batrachochytrium dendrobatidis and Batrachochytrium salamandrivorans) and ranavirus diseases due to viruses of the genus Ranavirus in the family Iridoviridae. Other pathogens and parasites also afflict amphibians, but here I will limit myself to a review of recent literature linking stress and these emerging diseases (chytridiomycosis and ranavirus disease) in order to better predict how environmental stressors and disease will affect global amphibian populations.     

皮质酮与慢性不可预见性应激诱导的两种抑郁症模型比较

目的从行为学及分子水平比较皮质酮(CORT)与慢性不可预见性应激(CUMS)诱导的抑郁症模型的异同,为抑郁症发病机制研究及抗抑郁药物的筛选与评价模型提供一定的参考。方法将30只雄性C57BL/6小鼠随机分成对照组(Ctrl)、慢性不可预见应激组(CUMS)和皮质酮注射应激组(CORT)组,制作应激模型21d,期间每3d对小鼠进行称重。21d模型制作结束后,对小鼠进行行为学测试,并于第22天,通过眼眶取血收集动物血清,并用ELISA法测定血清皮质酮含量。眼眶取血后脱颈椎处死动物,取出动物的胸腺和脾脏进行称重,计算脏器指数;取出脑组织,置于液氮罐保存,尼氏(Nissl)染色法观察小鼠大脑海马区神经元损伤情况;采用Western blotting、RT-PCR方法测定抑郁症相关蛋白及基因的表达。结果与对照组相比,两种抑郁症模型组开场实验中的行为学指标均改变,强迫游泳和悬尾实验的累积不动时间显著升高。两个模型组的胸腺指数无明显变化,而CORT组的脾脏指数较对照组下降。CUMS和CORT组小鼠血清皮质酮含量高于对照组,CORT组与CUMS组相比有升高趋势,但差异无显著性。CUMS和CORT两种模型均使海马CA1、CA3和DG区神经元密度降低,CORT模型变化更明显。两模型组的促肾上腺素释放激素(CRH)的mRNA和蛋白的表达量均显著性增加,脑源性神经营养因子(BDNF)、磷酸化转录因子环磷腺苷反应元件结合蛋白(p-CREB)和磷酸化细胞外信号调节激酶(p-ERK)的蛋白表达水平均呈现明显地抑制,但CUMS和CORT两组之间差异无显著性。结论 CORT模型和CUMS模型均能成功构建抑郁症模型,且与下丘脑-垂体-肾上腺(HPA)轴紊乱有关,两种模型在小鼠海马结构改变及大脑BDNF-pCREB和ERK信号通路激活等方面差异无显著性。提示,CORT模型可用于抑郁症机制的研究及抗抑郁药的筛选与评价,尤其可用于以HPA轴功能紊乱所引起的抑郁症分子机制探讨。     

Brain and pineal 7α-hydroxypregnenolone stimulating locomotor activity: Identification,mode of action and regulation of biosynthesis

Biologically active steroids synthesized in the central and peripheral nervous systems are termed neurosteroids. However, the biosynthetic pathways leading to the formation of neurosteroids are still incompletely elucidated. 7α-Hydroxypregnenolone, a novel bioactive neurosteroid stimulating locomotor activity, has been recently identified in the brain of newts and quail. Subsequently, the mode of action and regulation of biosynthesis of 7α-hydroxypregnenolone have been determined. Moreover, recent studies on birds have demonstrated that the pineal gland, an endocrine organ located close to the brain, is an important site of production of neurosteroids de novo from cholesterol. 7α-Hydroxypregnenolone is a major pineal neurosteroid that stimulates locomotor activity in juvenile chickens, connecting light-induced gene expression with locomotion. This review summarizes the advances in our understanding of the identification, mode of action and regulation of biosynthesis of brain and pineal 7α-hydroxypregnenolone, a potent stimulator of locomotor activity.     

Central regulation of blood pressure by the mineralocorticoid receptor

Addition of mineralocorticoid receptor (MR) antagonists to standard therapy for heart failure, kidney disease, metabolic syndrome, and diabetes is increasing steadily in response to clinical trials demonstrating clear benefits. In addition to blocking deleterious activity of MR within the heart, vessels and kidneys, MR antagonists target MR in hemodynamic regulatory centers in the brain, thereby decreasing excessive sympathetic nervous system drive, vasopressin release, abnormal baroreceptor function, and circulating and tissue pro-inflammatory cytokines. However, brain MR are also involved with cognition, memory, affect and functions yet to be determined. Understanding specific central mechanisms involved in blood pressure regulation by MR is necessary for the development of agents to target downstream events specific to central hemodynamic regulation, not only to avoid the hypokalemia caused by inhibition of renal tubular MR, but also to avoid untoward long term effects of inhibiting brain MR that are not involved in blood pressure control.