自然发生的棕色田鼠不同水平的社会性形成和调节的神经内分泌机制

发布时间：2017-12-27 22:37

本文关键词：自然发生的棕色田鼠不同水平的社会性形成和调节的神经内分泌机制　出处：《陕西师范大学》2016年博士论文　论文类型：学位论文

【摘要】：健康的社会交往和稳定的社会联系能力的减弱是许多精神疾病如抑郁症,成瘾,精神分裂症和自闭症等普遍的症状之一。理解正常社会联系发育、形成的神经生物机制和遗传机制对理解上述这些精神疾病非常重要,也可为药理干预和治疗这些疾病提供可能的靶标。社会联系在生命活动中普遍存在,它可以影响社会、心理、生理和行为机能。关于社会联系的发育形成机制目前还不清楚,但是社会联系涉及一系列复杂的过程,包括通过感觉发现同伴、识别熟悉的个体以及产生接近或接触的动机。此外,必须抑制如厌恶或攻击等其他不利于社会联系的行为。许多关于动物和人类的研究已经发现加压素、催产素和多巴胺可以调节复杂的社会联系。然而,这其中大多数的报道都集中在研究加压素、催产素和多巴胺与和繁殖相关的社会联系上,比如关于加压素、催产素和多巴胺对亲本行为和配偶联系的调节。但是关于加压素、催产素和多巴胺与非繁殖目的的社会联系的研究报道还很有限。而且,生命早期社会经历的改变可以对幼崽脑和行为产生长期的影响。早期社会环境的改变可以引起加压素、催产素和多巴胺系统的改变,从而产生生理功能的系统性变化,这种变化是通过与繁殖有关的社会行为如亲本行为和配偶联系的变化体现的。但是早期社会环境的改变对非繁殖目的的社会联系以及与之相关的神经内分泌机制的长期影响仍然不清楚。另外,想全面的解释中枢加压素、催产素和多巴胺对社会联系的所有影响是很困难的,因为这些神经递质或调质常常具有物种和/或性R%特异性,而且它们对社会联系的影响在不同脑区是不同的。已经有大量的证据表明在中枢神经系统的特异位点注射加压素、催产素和多巴胺可以对与繁殖有关的社会联系产生显著的影响。研究也表明具有加压素、催产素和多巴胺受体的脑区比如伏核、杏仁内侧核等也调节着与社会联系相关的行为。那么加压素、催产素和多巴胺系统到底和动物的社会性有什么联系?早期的发育环境是否可通过改变加压素、催产素和多巴胺系统进而影响成年后的社会行为?这三个系统到底通过哪些脑区发挥作用?本研究以具有复杂社会性的单配制棕色田鼠为动物模型,探讨社会性形成和调节的神经内分泌机制,本研究有三个目的,首先,比较自然发生的不同社会性水平的棕色田鼠,其脑内加压素、催产素和多巴胺系统参数的表达是否存在差异;第二,棕色田鼠自然发生的不同水平的亲本投资是否对社会性和加压素、催产素和多巴胺系统的水平产生影响。第二,以棕色田鼠为模型观察催产素能否在伏核对个体的社会行为起到促进作用,并且观察这种效应是否有性别依赖性,并研究催产素是否能够在伏核影响棕色田鼠的焦虑和运动水平。(1)棕色田鼠自然发生的不同水平的社会性与中枢多巴胺、加压素和催产素的水平及相应的多巴胺D1和D2受体、加压素V1a受体及催产素受体水平的关系:研究发现相对于低社会性的棕色田鼠,具有高社会性的田鼠室旁核(PVN)和视上核(SON)具有高水平的催产素阳性神经元,在腹侧被盖区(VTA)具有高水平的酪氨酸羟化酶(TH)阳性颗粒;而在高社会性雄性田鼠PVN具有较少的加压素阳性神经元。另一方面,在高社会性田鼠的伏核发现有更多的催产素受体的表达,并且发现高社会性雄性田鼠在伏核多巴胺D1和D2受体的具有低水平表达量,而高社会性雌鼠具有较少的伏核D2受体表达,而在杏仁内侧核则较高的D2受体的表达。(2)棕色田鼠自然发生的不同水平的亲本投资对社会性和脑内多巴胺、加压素和催产素水平及多巴胺D1和D2受体、加压素V1a受体和催产素受体表达量的影响:研究发现接受高水平亲本投资的雌性和雄性棕色田鼠的社会性明显升高,这说明早期亲本投资如预期的一样可以影响棕色田鼠非繁殖目的的社会行为。同时,发现接受高水平亲本投资的田鼠室旁核(PVN)和视上核(SON)发现增多的催产素阳性颗粒,在腹侧被盖区(VTA)发现增多的酪氨酸羟化酶(TH)阳性颗粒,而接受高水平亲本投资的雄鼠室旁核发现减少的加压素阳性颗粒。此外,研究还发现早期高水平的亲本投资可以显著增加伏核催产素受体的表达量,降低雄鼠伏核D1R and D2R mRNA的表达;抑制雌鼠伏核D2R的表达以及增加雌鼠杏仁内侧核D2R的表达量。(3)在伏核注射催产素及其受体拮抗剂对社会接近行为的影响:研究发现在低社会性雌性和雄性棕色田鼠伏核内微注射催产素可以提高其社会性,而这种影响具有剂量依赖效应。结果显示伏核每侧注射1ng催产素可以增加社会偏好,然而这种影响在较低和较高的剂量中没有发现。伏核注射催产素受体拮抗剂,阻断伏核内催产素与其受体的结合,则可以减少雌性和雄性棕色田鼠的社会偏好,这种影响也具有剂量依赖效应,伏核每侧微注射催产素受体拮抗剂10ng和100ng都可以减少社会接近行为,但是注射1ng的拮抗剂则没有效果。但是在伏核注射催产素或催产素受体拮抗剂在任何剂量(0.1-10ng/side or 1-100ng/side)都没有影响棕色田鼠在旷场实验中的行为。总之,本研究可以得出这样的结论:催产素、加压素和多巴胺系统可以以性别特异性和脑区特异性的方式调节非繁殖目的的社会行为,自然发生的不同亲本投资不但影响成年后的社会性,同时改变了相关脑区催产素、加压素和多巴胺系统参数的水平,说明早期的不同水平的亲本投资可能通过改变这些神经化学物质系统影响着成年后的社会性。此外,研究发现伏核是催产素影响社会性的一个重要脑区。这些研究结果在一定程度上阐明了社会性发育、形成和调节的神经内分泌机制。为不同性别低水平社会性或社交障碍等异常行为的预防和治疗提供新思路。
[Abstract]:The weakening of healthy social interaction and stable social connections is one of the most common symptoms of many mental disorders such as depression, addiction, schizophrenia and autism. Understanding the mechanism and genetic mechanism of normal social connections and development is very important for understanding these mental disorders, and it also provides a possible target for pharmacological intervention and treatment of these diseases. Social connections are common in life activities, which can affect social, psychological, physiological and behavioral functions. The mechanism of the development of social connections is not clear yet, but social connections involve a series of complex processes, including finding companions through feeling, identifying familiar individuals and generating motivation for approaching or contacting. In addition, other acts such as disgust or attack that are not conducive to social connections must be suppressed. Many studies on animals and humans have found that vasopressin, oxytocin, and dopamine can regulate complex social connections. However, most of these reports are focused on the study of vasopressin, oxytocin and dopamine, and the social connections related to reproduction, such as vasopressin, oxytocin and dopamine, which regulate the behavior of parents and their spouses. But there are limited reports on the social links between vasopressin, oxytocin and dopamine and non reproductive purposes. Moreover, changes in early life experience can have a long-term impact on the baby's brain and behavior. Changes in early social environment can cause changes in vasopressin, oxytocin and dopamine system, resulting in systemic changes in physiological function. This change is reflected through reproductive changes related to social behaviors, such as parental behavior and spousal connections. However, the changes in the early social environment are still unclear about the social connections of non reproductive purposes and the long-term effects of the related neuroendocrine mechanisms. In addition, it is difficult to fully explain all the effects of central vasopressin, oxytocin and dopamine on social connections, because these neurotransmitters or conditioner often have R% specificity of species and / or sex, and their effects on social connections are different in different brain regions. There has been a lot of evidence that injection of vasopressin, oxytocin and dopamine at the specific sites of the central nervous system can significantly affect the social connections related to reproduction. The study also showed that the brain regions with vasopressin, oxytocin, and dopamine receptors, such as the nucleus accumbens and the medial amygdala, also regulate the behavior associated with social connections. Then vasopressin, oxytocin and dopamine system in the end what is the relationship between social development and environment of the early animal? Whether hormone and dopamine system and thus affect the social behavior of adult by changing vasopressin, oxytocin? These three systems play a role in the end through which brain regions? In this study, with complex social single preparation of voles as animal models, to explore the social formation and regulation of the neuroendocrine mechanism, this study has three purposes, first, comparison of different naturally occurring social level of mandarin voles, compression element, different expression of oxytocin and dopamine system parameters in the brain; second, naturally occurring voles different levels of social and parental investment whether vasopressin, oxytocin and dopamine system influence. Second, we used Mandarin Microtus fortis as a model to observe whether oxytocin can promote the social behavior of individuals in volt nucleus, and observe whether this effect is gender dependent. We also study whether oxytocin can affect the anxiety and motor level of vole in vole. (1) the relationship between social and different levels of dopamine, vasopressin and oxytocin levels and corresponding dopamine D1 and D2 receptor, vasopressin V1a receptor and oxytocin receptor levels of Microtus mandarinus naturally occurring: the study found that compared to the low social mandarin voles, has high social side room vole nuclear (PVN) and supraoptic nucleus (SON) with high levels of oxytocin immunoreactive neurons in the ventral tegmental area (VTA) with high levels of tyrosine hydroxylase (TH) positive granules; with vasopressin positive neurons less in high social male voles PVN. On the other hand, in the high social vole found expression in nucleus accumbens more oxytocin receptor, and found that high social male voles in the nucleus accumbens dopamine D1 and D2 receptors with low expression and high expression level, social female rats with less D2 receptor in the nucleus accumbens, apricot kernel inside nuclear D2 receptor expression was higher. (2) voles naturally occurring at different levels of dopamine, parental investment on social and brain levels of vasopressin and oxytocin and dopamine D1 and D2 receptors, pressure effect on expression of angiotensin V1a receptor and oxytocin receptor: the study found that the social acceptance of high levels of parental investment of female and male voles significantly this shows that early parental investment increased, as expected can affect the social behavior of voles in non breeding purposes. At the same time, found room voles receive high levels of parental investment (PVN) in the paraventricular nucleus and the supraoptic nucleus (SON) found an increase in oxytocin positive particles in the ventral tegmental area (VTA) found an increase in tyrosine hydroxylase (TH) positive particles, and receive high levels of parental investment in male rat paraventricular nucleus found vasopressin positive granules reduced. In addition, the study also found that early high parental investment significantly increased the expression of oxytocin receptor in nucleus accumbens, reduced the expression of D1R and D2R mRNA in male rats, inhibited the expression of D2R in the nucleus accumbens of female rats and increased the expression of D2R in the medial amygdaloid nucleus of female rats. (3) the effects of oxytocin and its receptor antagonists on social proximity behavior in nucleus accumbens: it is found that microinjection of oxytocin in low social female and male vole voles can improve their social performance.
【学位授予单位】：陕西师范大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：Q42

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