Effects of olfactory bulb removal on fear responses and passive avoidance in the rat

Following complete bulbectomies, male hooded rats showed an increase in irritability and difficulty of handling, but a decrease in timidity or fear responses. After rats had learned to drink in an open field, a cat was confined in the center, and fear was defined by the behavior of controls, viz., almost total suppression of drinking and long periods of freezing, broken by brief bursts of high-speed activity. Bulb animals could not have differed more radically. Bulbs showed neither freezing nor suppression of drinking. The present results could not be attributed to differences in shock reactivity; nor could they be attributed to differences in learning or retention. Bulb animals also showed an impairment on the acquisition of step-down passive avoidance but no difference in step-downs after acquisition. These results argue against an impairment of response inhibition. The present study suggests that bulbectomy increases irritability and decreases timidity.     

Social stress and reproductive success in the female Syrian hamster: endocrine and behavioral correlates

In many mammal species, reproduction is not shared equally among the members of a social unit. Even though reproductive skew seems unlikely in females of solitary species, this phenomenon could result from environmental factors. Although solitary in the wild, captive Syrian hamsters (Mesocricetus auratus) are generally housed in groups. We investigated whether social stress produces some degree of reproductive skew in this solitary species and whether female reproductive success varies as a function of social rank. To assess the physiological relationship between social stress and fertility, we monitored reproductive hormones and glucocorticoids of solitary and pair-housed females during pregnancy by means of recently established non-invasive methods for measuring hormone metabolites in the feces. The patterns of fecal progesterone, estrogen and glucocorticoid metabolites were similar to those found in blood and reported in the literature for pregnant hamsters. As expected, dominant females had higher breeding success than subordinate females. However the rate of reproductive failure was also very high among the singly housed females of our control group. The number of pups per litter, the average sex-ratio in each group, and the mean weight of pups did not differ significantly among groups. Glucocorticoid concentrations were unaffected by housing and social rank and the few differences between the endocrine profiles of singly- and pair-housed females are not sufficient to explain the observed difference in breeding success. It is likely that social isolation impairs reproduction in the same manner as subordination. Our findings suggest that social isolation of animals accustomed to group living was equally as disturbing as cohabitation with an unknown conspecific.     

Enhanced fear recall and emotional arousal in rats recovering from chronic variable stress

Emergence of posttraumatic-like behaviors following chronic trauma is of interest given the rising prevalence of combat-related posttraumatic stress disorder (PTSD). Stress associated with combat usually involves chronic traumatization, composed of multiple, single episode events occurring in an unpredictable fashion. In this study, we investigated whether rats recovering from repeated trauma in the form of chronic variable stress (CVS) express posttraumatic stress-like behaviors and dysregulated neuroendocrine responses. Cohorts of Long-Evans rats underwent a 7 day CVS paradigm followed by behavioral and neuroendocrine testing during early (16 h post CVS) and delayed (7 day) recovery time points. A fear conditioning-extinction-reminder shock paradigm revealed that CVS induces exaggerated fear recall to reminder shock, suggestive of potentiated fear memory. Rats with CVS experience also expressed a delayed expression of fearful arousal under aversive context, however, social anxiety was not affected during post-CVS recovery. Persistent sensitization of the hypothalamic-pituitary-adrenocorticotropic response to a novel acute stressor was observed in CVS exposed rats. Collectively, our data are consistent with the constellation of symptoms associated with posttraumatic stress syndrome, such as re-experiencing, and arousal to fearful contexts. The CVS-recovery paradigm may be useful to simulate trauma outcomes following chronic traumatization that is often associated with repeated combat stress.     

Hormonal responses accompanying fear and agitation in the squirrel monkey

The adrenocortical and gonadal responses of 14 male monkeys were evaluated during four experimental conditions in order to evaluate the influence of social interactions on endocrine responsiveness. Plasma hormone levels were determined during the establishment of social relations, after 60-min exposures to a novel environment, after 60-min exposures to a snake, and 60 min after ACTH administration. Both adrenal and gonadal secretion changed significantly during the first day after social relations were established, although only dominant males showed increases in testosterone, whereas cortisol levels rose in all subjects. Increases in cortisol, but not testosterone, were also observed following exposure to novelty or a snake. The presence of a social partner reduced signs of behavioral disturbance during these test conditions, although the adrenal responses were equivalent or greater than when tested alone. This finding qualifies earlier research which indicated that social support was beneficial for reducing stress when squirrel monkeys were tested in larger groups in their home environment.     

Differences in fear of falling in the elderly with or without dizzines

To compare prevalence and risk factors associated with fear of falling (FoF) in two groups of elderly people, 109 patients with recurrent dizziness and 109 controls without dizziness. FoF was defined as a positive response to the single question and with Falls Efficacy Scale of >50. The prevalence of FoF was greater (71.6%) in the dizzy group (control, 31.2%; p < 0.001). Factors associated with FoF in the dizzy-group were diabetes, high General Health Questionnaire (GHQ-28) score and poor balance score. In the non-dizzy group, female gender, high GHQ, and poor gait score in Tinetti's scale were the association. Further research is needed to explore the relationship between dizziness and FoF.     

Immune responses in the human female reproductive tract

Mucosal surfaces are key interfaces between the host and its environment, but also constitute ports of entry for numerous pathogens. The gut and lung mucosae act as points of nutrient and gas exchange, respectively, but the physiological purpose of the female reproductive tract (FRT) is to allow implantation and development of the fetus. Our understanding of immune responses in the FRT has traditionally lagged behind our grasp of the situation at other mucosal sites, but recently reproductive immunologists have begun to make rapid progress in this challenging area. Here, we review current knowledge of immune responses in the human FRT and their heterogeneity within and between compartments. In the commensal-rich vagina, the immune system must allow the growth of beneficial microbes, whereas the key challenge in the uterus is allowing the growth of the semi-allogeneic fetus. In both compartments, these objectives must be balanced with the need to eliminate pathogens. Our developing understanding of immune responses in the FRT will help us develop interventions to prevent the spread of sexually transmitted diseases and to improve outcomes of pregnancy for mothers and babies.     

Scientific principles of regenerative medicine and their application in the female reproductive system

The goal of regenerative medicine is to repair, replace, or regenerate diseased tissues/organs in order to restore normal function. In this paper we will first discuss the general principle of regenerative medicine and the various techniques and approaches that have been used to replace or regenerate cells in diseased tissues and organs. Then, we will review different regenerative medicine approaches that have been used to treat specific diseased tissues and organs of the reproductive system in both animal and human experiments. It is clear from this article that regenerative medicine holds significant promise, and we hope that the review will serve as a platform for further development of regenerative medicine technologies for the treatment of inadequacies of the reproductive system.     

重庆市北碚区育龄期妇女生殖健康调查与分析

目的对北碚区已婚育龄期妇女实行普查，了解该区已婚育龄期妇女生殖健康情况。方法采用妇科常规检查、阴道分泌物（悬滴法）、官颈刮片、盆腔X线透视和阴道B型超声检查等方法调查了北碚区已婚育龄期妇女90082例。结果调查对象中患妇科病人数为62859例，患病率为69．78％；农村妇女和城市妇女霉菌、滴虫及老年性阴道炎患病率之间的差异有显著性（P〈0．05）；农村妇女和城市妇女生殖器损伤性疾病患病率之间的差异有显著性（P〈0．05）；各年龄组各种疾病的患病率比较差异有显著性（P〈0．05），阴道炎、盆腔炎、性传播疾病随年龄增加而下降；不同妊娠次数的患宫颈炎、会阴裂伤的患病率比较差异有显著性（P〈0．05）。92．01％妇女曾在卫生保健机构咨询过可选择的避孕方法和适用时间。81．00％妇女使用一种或一种以上的避孕方式。结论已婚育龄妇女的妇科病患病率仍很高，在计划生育工作中应对其加强普查普治及生殖保健咨询；农村育龄妇女生殖健康服务基础薄弱，而农村妇女对生殖健康服务的需求迫切。     

Differential impact of the first and second wave of a stress response on subsequent fear conditioning in healthy men

Stress is a process of multiple neuroendocrine changes over time. We examined effects of the first-wave and second-wave stress response on acquisition and immediate extinction of differential fear conditioning, assessed by skin conductance responses. In Experiment 1, we placed acquisition either close to the (second-wave) salivary cortisol peak, induced by a psychosocial stressor (experimental group, EG), or after non-stressful pretreatment (control group, CG). Contrary to predictions, groups did not differ in differential responding. In the EG only, mean differential responding was negatively correlated with cortisol increases. In Experiment 2, we placed conditioning near the first-wave stress response, induced by a cold pressor test (CPT), or after a warm-water condition (CG). CPT-stress increased extinction resistance. Moreover, acquisition performance after CPT was positively correlated with first-wave blood pressure increases. Data suggest that mediators of the first-wave stress response enhance fear maintenance whereas second-wave cortisol responsivity to stress might attenuate fear learning.     

Role of conceptual knowledge in learning and retention of conditioned fear

Associating sensory cues with aversive outcomes is a relatively basic process shared across species. Yet higher-order cognitive processes likely contribute to associative fear learning in many circumstances, especially in humans. Here we ask whether fears can be acquired based on conceptual knowledge of object categories, and whether such concept-based fear conditioning leads to enhanced memory representations for conditioned objects. Participants were presented with a heterogeneous collection of images of animals and tools. Objects from one category were reinforced by an electrical shock, whereas the other category was never reinforced. Results confirmed concept-based fear learning through subjective report of shock expectancy, heightened skin conductance responses, and enhanced 24 h recognition memory for items from the conditioned category. These results provide novel evidence that conditioned fear can generalize through knowledge of object concepts, and sheds light on the persistent nature of fear memories and category-based fear responses symptomatic of some anxiety disorders.     

脐血铅与初乳铅含量与新生儿神经行为发育关系

目的 探讨在宫内低水平铅暴露状态下,新生儿脐血铅含量及初乳铅铅含量与神经行为发育的关系。方法 随机选取南京市妇幼保健院医院产科2010-01/04出生的足月新生儿170例。以脐血铅和初乳铅铅含量作为新生儿铅暴露的指标,新生儿神经行为（NBNA）发育评分作为效应指标,根据初乳铅中位数48.3μg/l,新生儿被分为高低铅两组。结果 高暴露组在新生儿主动肌张力、原始反射,和神经行为发育总评分上低于低暴露组,差异有统计学意义（P〈0.05）,在新生儿行为能力、被动肌张力、一般估价上差异无统计学意义。结论 初乳铅脐血铅水平和与婴儿的早期发育有关,铅可通过乳汁和脐血造成新生儿的铅接触,对新生儿婴儿早期神经行为发育产生不良影响。     

Opioid modulation of reflex versus operant responses following stress in the rat

In pre-clinical models intended to evaluate nociceptive processing, acute stress suppresses reflex responses to thermal stimulation, an effect previously described as stress-induced "analgesia." Suggestions that endogenous opioids mediate this effect are based on demonstrations that stress-induced hyporeflexia is enhanced by high dose morphine (>5 mg/kg) and is reversed by naloxone. However, reflexes and pain sensations can be modulated differentially. Therefore, in the present study direct comparisons were made of opioid agonist and antagonist actions, independently and in combination with acute restraint stress in Long Evans rats, on reflex lick-guard (L/G) and operant escape responses to nociceptive thermal stimulation (44.5 degrees C). A high dose of morphine (>8 mg/kg) was required to reduce reflex responding, but a moderate dose of morphine (1 mg/kg) significantly reduced escape responding. The same moderate dose (and also 5 mg/kg) of morphine significantly enhanced reflex responding. Naloxone (3 mg/kg) significantly enhanced escape responding but did not affect L/G responding. Restraint stress significantly suppressed L/G reflexes (hyporeflexia) but enhanced escape responses (hyperalgesia). Stress-induced hyperalgesia was significantly reduced by morphine and enhanced by naloxone. In contrast, stress-induced hyporeflexia was blocked by both naloxone and 1 mg/kg of morphine. Thus, stress-induced hyperalgesia was opposed by endogenous opioid release and by administration of morphine. Stress-induced hyporeflexia was dependent upon endogenous opioid release but was counteracted by a moderate dose of morphine. These data demonstrate a differential modulation of reflex and operant outcome measures by stress and by separate or combined opioid antagonism or administration of morphine.     

Acupuncture is effective to attenuate stress and stimulate lymphocyte proliferation in the elderly

Acupuncture has increasingly been used to treat many conditions, including psychiatric disorders and immunological-related disorders. However, the effects of acupuncture as stress management and immune functions in the elderly are largely unclear. Here we investigated the effects of acupuncture on stress-related psychological symptoms and cellular immunity in young adults and elderly subjects. The acupuncture treatment consisted of six sessions and the procedures included the insertion of needles at bilateral acupoints LI4, SP6 and ST36. Psychological variables (depression, anxiety and stress) were investigated by means of self-assessment inventories. Peripheral blood mononuclear cells were isolated and cultured in vitro to measure mitogen-induced T-cell proliferation as well as cellular sensitivity to dexamethasone. All data were assessed before and after the intervention. Acupuncture was able to significantly reduce depression (p < 0.001), anxiety (p < 0.001) and stress (p < 0.001) scores. The intervention also increased T-cell proliferation, with greater intensity in the elderly group (p = 0.004). No changes in cellular sensitivity to dexamethasone were observed following acupuncture. We conclude that acupuncture was efficient to attenuate the psychological distress as well as to increase an important feature of cellular immunosenescence.     

Early stress exposure impairs synaptic potentiation in the rat medial prefrontal cortex underlying contextual fear extinction

Traumatic events during early life may affect the neural systems associated with memory function, including extinction, and lead to altered sensitivity to stress later in life. We recently reported that changes in prefrontal synaptic efficacy in response to extinction trials did not occur in adult rats exposed to early postnatal stress (i.e. footshock [FS] stress during postnatal day 21–25 [3W-FS group]). However, identifying neurocircuitry and neural mechanisms responsible for extinction retrieval after extinction training have not been precisely determined. The present study explored whether synaptic transmission in the hippocampal-medial prefrontal cortex (mPFC) neural pathway is altered by extinction retrieval on the day after extinction trials using electrophysiological approaches combined with behavioral analysis. We also elucidated the effects of early postnatal stress on the synaptic response in this neural circuit underlying extinction retrieval. Evoked potential in the mPFC was enhanced following extinction retrieval, accompanied by reduced freezing behavior. This synaptic facilitation (i.e. a long-term potentiation [LTP]-like response) did not occur; rather synaptic inhibition was observed in the 3W-FS group, accompanied by sustained freezing. The behavioral deficit and synaptic inhibition observed in the 3W-FS group were time-dependently ameliorated by the partial N-methyl-d-aspartate (NMDA) receptor agonist d-cycloserine (15 mg/kg, i.p.). These findings suggest that the LTP-like response in the hippocampal-mPFC pathway is associated with extinction retrieval of context-dependent fear memory. Early postnatal stress appears to induce neurodevelopmental dysfunction of this neural circuit and lead to impaired fear extinction later in life. The present data indicate that psychotherapy accompanied by pharmacological interventions that accelerate and strengthen extinction, such as d-cycloserine treatment, may have therapeutic potential for the treatment of anxiety disorders, including posttraumatic stress disorder.     

Changes with age in rat central monoaminergic system responses to cold stress

Changes with age in responses to stress of certain central monoaminergic systems were investigated. Three groups of rats, 4, 18 and 29 months old, were exposed to cold and the effect of this stress on hypothalamic tyrosine hydroxylase, and on the metabolism of DA and 5HT in different brain regions was evaluated. Senescent rats were unable for several hours to compensate the loss of body heat. Corticosterone secretion however was equally stimulated. Hypothalamic tyrosine hydroxylase activity was enhanced in the young rats but not in the old ones. However, the two groups of senescent rats did not show the increase in HVA levels noted in striata of young rats 2 hours after cold exposure. In contrast, the 18 and 29-month-old rats presented enhanced serotonergic tonus, indicated by the greater increase in 5HIAA determined by stress.     

脐血铅含量与体格发育和智商发育的关系及影响因素分析(英文)

目的探讨在宫内低水平铅暴露状态下,新生儿脐血铅含量与神经行为发育的关系,研究目的是评价脐血铅对孕妇妊娠结局和4岁学龄前儿童的神经发育的影响。课题的研究现场选在南京市妇幼保健院医院产科、新生儿科、儿童保健科门诊。2005年10月至2006年10月共170名孕妇被随机选入我们的研究。所采血液和脐血铅测定使用电感耦合等离子体质谱(ICP-MS)法,106名4岁上面提及孕妇所生的子女被随防,随防率是97.25%。方法通过问卷调查和体格检查分别了解上述儿童的一般状况、生长发育情况。用韦克斯勒氏学龄前儿童智商测量量表测定儿童智商,多元线性回归分析脐血铅和学龄前儿童体格和智商的相关性。同时随机选取南京市妇幼保健院医院产科出生的足月新生儿170例。以脐血铅含量作为新生儿铅暴露的指标,新生儿神经行为(NBNA)发育评分作为效应指标,以脐血铅中位数49.7U/L被分为高低铅组。结果高暴露组在新生儿主动肌张力、原始反射,和神经行为发育总评分上低于低暴露组,差异有统计学意义,在新生儿行为能力、被动肌张力、一般估价上差异无统计学意义。根据智商测定揭示,低铅组的操作智商和言语智商明显高于高铅组(t=2.91,P<0.01;t=5.87,P<0.01)。结论脐血铅水平和与婴儿的早期发育有关,铅可通过脐血造成新生儿的铅接触,对新生儿婴儿早期神经行为发育产生不良影响。随着脐血铅水平的增加,学龄前期儿童总智商评分和操作智商评分下降,妊娠期脐铅暴露水平可能是学龄前期儿童总智商评分和操作智商评分降低的危险因素。     

超排卵对大鼠卵巢组织结构及生殖内分泌的影响

目的: 探讨超排卵对大鼠卵巢组织结构和生殖内分泌功能的影响,为临床合理使用超排卵提供理论依据。方法: 30只雌性SD大鼠随机分为3组: 实验A组接受孕马血清和人绒毛膜促性腺激素重复6次超排卵,实验B组 给予3次生理盐水注射及孕马血清和人绒毛膜促性腺激素重复3次超排卵,对照组接受6次生理盐水注射。15 d及30 d后分别处死各组一半大鼠,观察卵巢组织形态学变化,采用放射免疫法检测血清雌二醇(E₂)、卵泡刺激素(FSH)、黄体生成素(LH)水平,并计算FSH/LH水平,比较各组间的差异。结果: 实验A和B组大鼠卵巢始基卵泡和初级卵泡计数明显低于对照组(P<0.05),但各组大鼠体内血清基础激素水平无显著差异(P>0.05)。结论: 超排卵会引起大鼠卵巢的卵泡发育受限,且随着超排卵次数的增加而加重,但尚未导致生殖内分泌激素水平的显著改变。     

孕期应激对子代雌鼠成年后钙结合蛋白Parvalbumin和Calretinin表达的影响

目的　探讨孕期应激对子代雌鼠成年后钙结合蛋白阳性神经元表达的影响。 方法　6只SD孕鼠随机分为孕期应激组（PS组）和对照组（CON组）。PS组孕鼠在妊娠晚期接受限制性应激,CON组不给予孕期应激。子代成年后,PS组和CON组雌性子代随机分别又分为PS-S组,PS-NS组,CON-S组和CON-NS组（n均=6）。PS-S组和CON-S组动物先后接受限制性应激和冰水应激。动物在接受应激后均给与水和酒精喂养,用Western blot检测海马钙结合蛋白Parvalbumin（PV）和Calretinin（CR）蛋白的表达,进一步结合共聚焦免疫荧光组织化学方法检测PV和CR在海马CA1、CA3区和齿状回（dentate gyrus,DG）的表达。 结果　与CON-NS组相比,海马区PV和CR的蛋白表达在CON-S,PS-NS和PS-S组下降,以PS-S组表达最低。PV在海马CA1、CA3区和DG的免疫荧光结果与PV的蛋白表达呈一致性,免疫阳性细胞明显减少;而CR的表达除了在海马CA1区的PS-NS组略有升高外,在其余各组的表达均较减少。与CON-NS组相比,PV和CR在其它各组的蛋白表达和免疫阳性细胞计数差异有统计学意义,其中以PS-S组的表达降低最为有统计学意义（P<0.05）。 结论　孕期应激可影响子代雌鼠成年后海马结构钙结合蛋白PV和CR的表达。     

Effects of litter‐overlapping on emotionality,stress response,and reproductive functions in male and female rats

In rats, mating at postpartum estrus and delayed dispersal of the young would result in the overlapping of two different‐age litters. As a consequence, newborn pups' early experience will include not only that acquired during the interaction with the mother and age‐matched littermates, but also with older siblings. As early‐life experience modulates rodents' brain function, behavior and reproduction, we aimed to assess how changes in the early environment provoked by the overlapping of litters would affect emotionality, stress response and reproductive functions of male and female pups during adulthood. Results showed that both male and female overlapped reared pups exhibited a reduced behavioral inhibition in the open field test during adulthood. In addition, overlapped reared adult females, but not males, showed a blunted corticosterone response to an acute stressor during diestrus and a reduction in sexual behavior. In summary, natural changes in early experience provoked by the overlapping of litters, long‐term modulate affective and reproductive behaviors, and the endocrine stress response in a sex dimorphic manner. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 51: 259–267, 2009