小型田鼠:研究单配制进化与调控的模型

哺乳动物的单配制通常被认为是社会性单配制,它不是单纯地由性行为来决定,而是由诸多因素,包括长期的pair bond、夫妻双方共同抚育后代、免近亲交配以及雌雄两性相似等来决定的。在这篇综述中,我们论述了如何以啮齿类田鼠属(Microtus)为模型,通过比较研究来帮助我们理解社会性单配制的进化以及其神经调控机制。对田鼠属的研究不仅证实了单配制起源于艰苦的生存条件的假说,而且还证实了雌性性选择可能有利于维持单配制。不仅如此,哺乳动物单配制的进化还需要雄性的prosocial行为的不断强化。例如,亲近行为可以促进pairbond的形成并强化雄性对后代的哺育行为,而这种强化则来源于神经多肽催产素(OT)和加压素(AVP)与类固醇类激素的相互作用。催产素和加压素调控pairbond和双亲哺育行为的表达,而单配制和多配制田鼠的催产素和加压素受体在脑内的分布有显的不同。比较研究揭示了小型田鼠单配制的调控机制,而种内差异和行为上的可塑性则有助于我们进一步理解这种机制。比如,在某些条件下,多配制的草原田鼠(Microtus pennsylvanicu)的雄性个体具有哺育后代的行为。尽管草原田鼠的加压素Vla受体在脑内的分布与其他多配制的田鼠相似,但是如果脑室注射加压素,仍可以诱发其哺育后代的行为。同样是单配制的橙腹田鼠(Microtus ochrogaster),生活在：Illnois的显示出高水平的prosocial行为,而生活在Kansas的则表现出较低水平的社会性行为。即使两个种群的催产素或加压素Vla受体在脑内的分布相同,它们的雌激素受体表达水平显不同,这在雄性个体表现尤其明显。与Kansas的雄性个体相比,在终纹床核(bed rucleus of the stria tenninalis)和杏仁核中区(medial amygdala)这两个调控亲近行为和攻击行为的脑区,Illinois的雄性个体的α雌激素受体的水平要低得多。这些研究表明对雌激素的低敏感程度有利于高水平地表达prosocial行为并降低特定类型的攻击行为。     

雌雄子午沙鼠的认知行为及其神经内分泌水平的差异

本研究通过对雌雄子午沙鼠进行新物体识别和社会认知实验,运用免疫组化方法检测其相关脑区合成催产素（OT）、加压素（AVP）和多巴胺（DA）能的神经元数量,采用酶联免疫试验（ELISA）方法检测了其血清中OT、AVP的水平,探究了雌雄子午沙鼠的两性认知差异及其神经内分泌水平的差异。结果表明,雌雄子午沙鼠对新物体的探究时间均要显著高于旧物体,雌雄子午沙鼠的辨别指数无显著差异（P＞0.05）;雄性子午沙鼠随着探究次数的增加对重复刺激鼠a的探究时间不断减少,对陌生刺激鼠b的探究时间显著高于刺激鼠a（P＜0.05）;雌性子午沙鼠没有此趋势。雄性子午沙鼠OT能神经元数量在下丘脑室旁核(PVN)和视上核(SON)均要显著少于雌性（P＜0.05）;雄性个体DA能神经元数量在黑质显著高于雌性（P＜0.01）;然而雄性个体DA能神经元数量在腹侧被盖区显著少于雌性（P＜0.01）;雌雄子午沙鼠血清OT、AVP水平均无显著差异。综上所述,雌雄子午沙鼠对新物体的识别能力无显著差异,然而雄性子午沙鼠的社会认知能力强于雌性。在神经内分泌水平上,雌雄子午沙鼠PVN和SON中OT能神经元数量、黑质和腹侧背盖区的DA能神经元数量均呈现出了两性差异。     

青春期社会奖赏行为性别差异的催产素和多巴胺调控机制

社交互动的奖励特性对于社会行为的表达和适应性社会关系的发展至关重要。当个体受到应激时会导致奖赏系统异常而缺乏社会交往,出现情绪障碍并具有性二态。青春期发育中社会奖赏行为存在显著的性别差异,男性对社会奖赏敏感性大于女性;相反,女性对社会惩罚的敏感性高于男性。在青春期发育过程中,催产素/加压素(OT/AVP)、多巴胺(DA)系统在奖赏环路的性别差异及OT/AVP受体基因表达的多态性,是奖赏行为及情绪障碍性二态的原因,揭示OT-社会奖赏-情绪障碍性二态三者交互作用的神经机制,对开展精神疾病治疗有重要指导意义。     

社会性单配制鸟类婚外父权的发生和影响因素

一雌一雄单配制鸟类中,雌性个体与配偶外雄性发生交配的行为称为婚外交配,继而导致了婚外受精产生婚外子代的现象称为产生了婚外父权。婚外父权广泛存在于鸟类中,针对其发生和影响因素已经成为了鸟类行为生态学研究的热点。本文收集了近十年社会性单配制鸟类婚外父权方面的研究文献,从婚外父权的发生及其影响因素两个方面综述了单配制鸟类婚外父权的研究进展。婚外父权发生原因的探讨主要包括：1、从两性的角度探讨雌雄两性在婚外行为中不同的进化繁殖策略。雄性策略旨在增加自身的繁殖输出;有关雌性策略则提出了确保受精假说、食物供给假说、遗传利益假说等,但目前尚存争议;2、在遗传利益假说中较常见的又分为3个假说：“优秀基因”假说、“遗传相容性”假说和“遗传多样性”假说,该三种假说是针对雌性从遗传方面获得的利益而提出的,不断有报道指出雌性配偶选择会被潜在的雄性遗传特性所影响;3、非遗传利益——母系效应影响婚外父权的进化。一些研究指出遗传质量参数,如体重、身体大小、存活率和免疫应答等方面可能会存在母系效应。婚外父权发生的影响因素这里主要指环境因素,包括繁殖同步性、繁殖密度、栖息地环境、产卵及孵化时机等。由于物种不同,受到环境压力不同,导致婚外父权发生率千差万别。最后本文针对未来的研究方向做出了展望。尽管近十年的研究进一步解释了鸟类婚外父权现象,但是该领域仍然存在并且产生了许多新的未解决的问题,而相关实验操作和理论的完善是深入探讨这些问题的关键。     

哺乳动物季节性繁殖的神经内分泌调节机制

动物的季节性繁殖,是指其繁殖活动从静止到复苏的一个年周期性循环。研究显示,kisspeptin和RFRP对繁殖的季节性变化具有重要作用。非繁殖期最显著的特点是雌激素对GnRH分泌的负反馈效应的增加,而雌激素的这种效应是由kisspeptin神经元传导的。因此,kisspeptin是影响繁殖活动的一个重要因子。RFRP的表达依赖于褪黑激素的分泌并呈现出季节性变化,在非繁殖期对繁殖活动的抑制作用非常明显。此外,甲状腺激素在繁殖期的终止上发挥着至关重要的作用,而多巴胺能神经元A14/A15也促进了雌激素负反馈效应的季节性变化。这些神经元系统通过协同作用一起调节了生殖功能随光周期的季节性转变。文章对繁殖的季节性和这4个神经内分泌系统之间的关系进行了系统的阐述。     

哺乳动物季节性繁殖的神经内分泌调节机制

动物的季节性繁殖, 是指其繁殖活动从静止到复苏的一个年周期性循环。研究显示, kisspeptin和RFRP对繁殖的季节性变化具有重要作用。非繁殖期最显著的特点是雌激素对GnRH分泌的负反馈效应的增加, 而雌激素的这种效应是由kisspeptin神经元传导的。因此, kisspeptin是影响繁殖活动的一个重要因子。RFRP的表达依赖于褪黑激素的分泌并呈现出季节性变化, 在非繁殖期对繁殖活动的抑制作用非常明显。此外, 甲状腺激素在繁殖期的终止上发挥着至关重要的作用, 而多巴胺能神经元A14/A15也促进了雌激素负反馈效应的季节性变化。这些神经元系统通过协同作用一起调节了生殖功能随光周期的季节性转变。文章对繁殖的季节性和这4个神经内分泌系统之间的关系进行了系统的阐述。     

神经调节素对大鼠脑缺血再灌注损伤后炎症反应的抑制作用和机制研究

目的：研究神经调节素及基质金属蛋白酶-9对于小鼠大脑缺血再灌注损伤后炎症反应的抑制作用和机制。方法：选取100只成年雄性大鼠,随机分成对照和治疗组。采用线栓方法由颈内到颈外进行插线处理,造成大脑中动脉处于闭塞状态的再灌注动物模型。治疗组颈动脉进行注射少量NRG-1β干预性治疗,通过氯化三苯基四氮唑（TTC）检查脑梗塞范围,细胞凋亡采用原住脱氧核糖核苷酸末端转移酶介导缺口末端进行标记,采用免疫组织化学、免疫荧光双标记法及免疫印迹法观察脑组织基质金属蛋白酶-9（MMP-9）表达。结果：脑缺血再灌注损伤后,随时间延长及缺氧,对照组大鼠大脑皮质和纹状体区脑组织细胞凋亡,并且胶质细胞MMP-9蛋白表达逐渐增加。治疗组大鼠经注射NRG-1β干预性治疗后,缺血脑组织梗死范围及其细胞凋亡数量相对呈明显下降趋势。胶质细胞MMP-9表达呈降低趋势。结论：大鼠脑缺血再灌注损伤后体内NRG-1β抑制胶质细胞MMP-9的表达,控制缺血脑组织梗死的范围并抑制正常细胞的凋亡,发挥了重要的抗炎作用,可作为对于大脑缺血再灌注损伤的研究新靶点。     

Neuropeptidergic regulation of affiliative behavior and social bonding in animals

Social relationships are essential for maintaining human mental health, yet little is known about the brain mechanisms involved in the development and maintenance of social bonds. Animal models are powerful tools for investigating the neurobiological mechanisms regulating the cognitive processes leading to the development of social relationships and for potentially extending our understanding of the human condition. In this review, we discuss the roles of the neuropeptides oxytocin and vasopressin in the regulation of social bonding as well as related social behaviors which culminate in the formation of social relationships in animal models. The formation of social bonds is a hierarchical process involving social motivation and approach, the processing of social stimuli and formation of social memories, and the social attachment itself. Oxytocin and vasopressin have been implicated in each of these processes. Specifically, these peptides facilitate social affiliation and parental nurturing behavior, are essential for social recognition in rodents, and are involved in the formation of selective mother-infant bonds in sheep and pair bonds in monogamous voles. The convergence of evidence from these animal studies makes oxytocin and vasopressin attractive candidates for the neural modulation of human social relationships as well as potential therapeutic targets for the treatment of psychiatric disorders associated with disruptions in social behavior, including autism.     

Developmental effects of oxytocin on neural activation and neuropeptide release in response to social stimuli

Previous studies have revealed that the neuropeptide hormone oxytocin (OT) has developmental effects on subsequent social behavior and on mechanisms underlying social behavior such as OT neurons and estrogen receptor alpha. This suggests that OT might also have developmental effects on neural responses to social stimuli. This was tested in socially monogamous prairie voles (Microtus ochrogaster) by manipulating OT on the first day of life and then assessing the response to a heterosexual pairing in adulthood. The response to cohabitation was assessed by quantifying neural activation in regions of the brain associated with sociosexual behavior and anxiety using c-Fos immunoreactivity. Additionally, immunocytochemistry was used to label OT and vasopressin neurons and plasma was assayed for both neuropeptides. Treatment effects were evident in females, but not in males. Blockade of OT receptors with an OT antagonist on the first day of life resulted in neural activation of the central amygdala in response to a pairing with a novel male in adulthood. The central amygdala does not normally express c-Fos after a heterosexual pairing in reproductively na?ve prairie voles. Treatment effects also were observed in vasopressin immunoreactivity in the SON with OT-treated females showing a decrease.     

Disruption of Parenting Behaviors in California Mice,a Monogamous Rodent Species,by Endocrine Disrupting Chemicals

The nature and extent of care received by an infant can affect social, emotional and cognitive development, features that endure into adulthood. Here we employed the monogamous, California mouse (Peromyscus californicus), a species, like the human, where both parents invest in offspring care, to determine whether early exposure to endocrine disrupting chemicals (EDC: bisphenol A, BPA; ethinyl estradiol, EE) of one or both parents altered their behaviors towards their pups. Females exposed to either compound spent less time nursing, grooming and being associated with their pups than controls, although there was little consequence on their weight gain. Care of pups by males was less affected by exposure to BPA and EE, but control, non-exposed females appeared able to “sense” a male partner previously exposed to either compound and, as a consequence, reduced their own parental investment in offspring from such pairings. The data emphasize the potential vulnerability of pups born to parents that had been exposed during their own early development to EDC, and that effects on the male, although subtle, also have consequences on overall parental care due to lack of full acceptance of the male by the female partner.     

Effects of Morris water maze testing on the neuroendocrine stress response and intrahypothalamic release of vasopressin and oxytocin in the rat

Adult male Wistar rats were trained in the Morris water maze (MWM) on 3 consecutive days to find a visible platform. Concomitantly, microdialysis samples from the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei were collected in order to monitor local release of the neuropeptides vasopressin (AVP) and oxytocin (OXT), respectively, during controllable swim stress. Additionally, a separate set of animals was equipped with chronic jugular venous catheters to collect blood samples for analyzing plasma concentrations of corticotropin (ACTH) and corticosterone during training in the MWM. As measured by microdialysis, swimming in the MWM caused a significantly increased release of AVP within the PVN and of OXT within the SON on each of the 3 test sessions. In contrast to OXT in the SON, basal AVP concentrations in the PVN tended to rise from day to day. Plasma ACTH and corticosterone were found to be similarly elevated in response to MWM exposure on each of the test sessions. Taken together, these data demonstrate that testing in the MWM is not only associated with a significant activation of the hypothalamo-pituitary-adrenal axis but also with an intrahypothalamic release of AVP and OXT. If compared with findings using repeated forced swimming as an uncontrollable stressor (Wotjak, C.T., Ganster, J., Kohl, G., Holsboer, F., Landgraf, R., Engelmann, M., 1998. Dissociated central and peripheral release of vasopressin, but not oxytocin, in response to repeated swim stress: new insights into the secretory capacities of peptidergic neurons. Neuroscience 85, 1209-1222), the present results suggest that (1) similarities in the release profiles of AVP in the PVN and plasma hormone levels are fairly independent from the controllability of the stressor and seem, thus, to primarily relate to the physical demands of the task, whereas (2) the different intra-SON OXT release profiles might be linked to the controllability of the stressor.     

Catecholamine biosynthesis and vasopressin and oxytocin secretion in the spontaneously hypertensive rat: an in vitro study of localized brain regions

The in vitro synthesis of catecholamines and the secretion of vasopressin (AVP) and oxytocin (OT) was measured in localized regions of the hypothalamo-neurohypophyseal system in the spontaneously hypertensive rat (SHR). The posterior pituitary (PP), median eminence (ME) and supraoptic (SON) and paraventricular (PVN) nuclear regions were incubated in vitro in media containing 3H-tyrosine. Media and tissue levels of AVP and OT were measured as well as norepinephrine and dopamine content and biosynthesis. There were no differences in peptide release in either the PP, ME or SON. However, there was a marked increase in peptide release from the PVN of the SHR. Media AVP levels were 0.3 pg/ml/micrograms protein in the WKY as compared to 2.1 pg/ml/micrograms protein in the SHR. OT release was increased 2 fold, from 0.85 to 1.7 pg/ml/micrograms protein. PVN content of both AVP and OT was significantly lower in the SHR. ME and SON peptide levels were not changed, while neurohypophyseal AVP levels were increased in the SHR. With regard to the catecholamines appreciable norepinephrine synthesis was measured in the PVN and SON while there was little 3H-norepinephrine in the ME or PP. In the hypertensive rat, there was an increase in norepinephrine synthesis in the PVN with no change in the SON. These results provide further support for fundamental changes in the catecholaminergic and peptidergic systems of the hypothalamo-neurohypophyseal axis of the SHR.     

Maintenance of pair bond during the non-reproductive season in a monogamous pipefish <Emphasis Type=Italic>Corythoichthys haematopterus</Emphasis>

During the non-reproductive season, male and female Corythoichthys haematopterus came to a particular site every early morning and performed a series of displays, called greetings, for a few minutes. After exchanging greetings, they had no further interactions during the daytime. This behavioural pattern was basically the same as that observed during the reproductive season. All greeting pairs bred in the following reproductive season if both members were present. These results indicate that mate fidelity of this pipefish is very high and that daily greetings lasting only a few minutes were enough to maintain pair bond all year around.     

Endogenous vasotocin exerts context-dependent behavioral effects in a semi-naturalistic colony environment

Arginine vasotocin (VT), and its mammalian homologue arginine vasopressin (VP), are neuropeptides involved in the regulation of social behaviors and stress responsiveness. Previous research has demonstrated opposing effects of VT/VP on aggression in different species. However, these divergent effects were obtained in different social contexts, leading to the hypothesis that different populations of VT/VP neurons regulate behaviors in a context-dependent manner. We here use VP antagonists to block endogenous VT function in male zebra finches (Taeniopygia guttata) within a semi-natural, mixed-sex colony setting. We examine the role of VT in the regulation of aggression and courtship, and in pair bond formation and maintenance, over the course of three days. Although our results confirm previous findings, in that antagonist treatment reduces aggressive mate competition during an initial behavioral session during which males encounter novel females, we find that the treatment effects are completely reversed within hours of colony establishment, and the antagonist treatment instead facilitates aggression in later sessions. This reversal occurs as aggression shifts from mate competition to nest defense, but is not causally associated with pairing status per se. Instead, we hypothesize that these divergent effects reflect context-specific activation of hypothalamic and amygdalar VT neurons that exert opposing influences on aggression. Across contexts, effects were highly specific to aggression and the antagonist treatment clearly failed to alter latency to pair bond formation, pair bond stability, and courtship. However, VT may still potentially influence these behaviors via promiscuous oxytocin-like receptors, which are widely distributed in the zebra finch brain.     

Nonself Recognition Through Intermolecular Disulfide Bond Formation of Ribonucleotide Reductase in Neurospora

Type I ribonucleotide reductases (RNRs) are conserved across diverse taxa and are essential for the conversion of RNA into DNA precursors. In Neurospora crassa, the large subunit of RNR (UN-24) is unusual in that it also has a nonself recognition function, whereby coexpression of Oak Ridge (OR) and Panama (PA) alleles of un-24 in the same cell leads to growth inhibition and cell death. We show that coexpressing these incompatible alleles of un-24 in N. crassa results in a high molecular weight UN-24 protein complex. A 63-amino-acid portion of the C terminus was sufficient for un-24^PA incompatibility activity. Redox active cysteines that are conserved in type I RNRs and essential for their catalytic function were found to be required for incompatibility activity of both UN-24^OR and UN-24^PA. Our results suggest a plausible model of un-24 incompatibility activity in which the formation of a complex between the incompatible RNR proteins is potentiated by intermolecular disulfide bond formation.     

CRF receptors in the nucleus accumbens modulate partner preference in prairie voles

Recent evidence suggests a role for corticotropin-releasing factor (CRF) in the regulation of pair bonding in prairie voles. We have previously shown that monogamous and non-monogamous vole species have dramatically different distributions of CRF receptor type 1 (CRF(1)) and CRF receptor type 2 (CRF(2)) in the brain and that CRF(1) and CRF(2) receptor densities in the nucleus accumbens (NAcc) are correlated with social organization. Monogamous prairie and pine voles have significantly lower levels of CRF receptor type 1 (CRF(1)), and significantly higher levels of type 2 (CRF(2)) binding, in NAcc than non-monogamous meadow and montane voles. Here, we report that microinjections of CRF directly into the NAcc accelerate partner preference formation in male prairie voles. Control injections of CSF into NAcc, and CRF into caudate-putamen, did not facilitate partner preference. Likewise, CRF injections into NAcc of non-monogamous meadow voles also did not facilitate partner preference. In prairie voles, this CRF facilitation effect was blocked by co-injection of either CRF(1) or CRF(2) receptor antagonists into NAcc. Immunocytochemical staining for CRF and Urocortin-1 (Ucn-1), two endogenous ligands for CRF(1) and CRF(2) receptors in the brain, revealed that CRF, but not Ucn-1, immunoreactive fibers were present in NAcc. This supports the hypothesis that local CRF release into NAcc could activate CRF(1) or CRF(2) receptors in the region. Taken together, our results reveal a novel role for accumbal CRF systems in social behavior.