VEGF调控抑郁症海马神经发生的研究进展

抑郁症是一种发生率高、易复发、危害大的精神障碍,其主要临床表现是持续的情绪低落和认知功能障碍.近年来其发病率越来越高,已经引起了人们广泛关注,由于其发病机制比较复杂,目前尚未完全阐明.神经营养假说认为,神经营养因子具有维持神经元生存、促进突触生长的作用,倘若前额叶、海马等脑区神经营养因子缺乏,可抑制相应脑功能从而最终导致抑郁;故抗抑郁药物治疗抑郁的途径是增加脑中的神经营养因子含量、提高突触可塑性和促进神经元生存.总之神经营养因子表达水平下降参与了抑郁症的病理生理过程.在众多神经营养因子中,VEGF是一种多功能的因子,能够通过多种途径促进血管生成,保护缺血和退变的神经元,引发成年大脑神经元再生,从而影响抑郁.而研究表明,成年海马神经发生与正在进行的血管生成是有着密切的联系.本文主要对VEGF在海马神经发生的作用机制及其调控对抑郁症的影响进行阐述.发现VEGF在调节海马神经发生具有重要的作用,并且VEGF及其下游信号参与了抑郁症的发生发展过程.     

催产素及其受体与哺乳动物的生殖

催产素（OT）是一种9肽激素,主要由哺乳动物下丘脑产生,以神经内分泌,旁分泌或自分泌形成,在哺乳动物生殖过程中发挥重要作用,催产素受体（OTR）是与G－蛋白相耦联的膜蛋白,通过激活磷脂酶C发挥其生理作用,OT在交配,分娩,哺池时由神经垂体（垂体后叶）脉冲式释放,促进子宫平滑肌和乳腺肌上皮细胞收缩,利用精子运行,胎儿娩出和射出乳汁,OT在中枢神经系统中参与调节母性行为,在性腺中促进某些物种的黄体形成,OT与PGF2a共同作用使有蹄动物黄体退化,以上过程都依赖于OT和OTR基因的时空特异性表达,多种激素参与它们的表达调控,但OT的生理作用有时也可被其它途径所替代。     

白兰氏鸡精减轻抑郁病症作用的研究

抑郁症是一类以情绪低落、乐趣丧失为核心症状的疾病。目前,临床研究发现,抑郁症往往伴随着昼夜节律的紊乱,但对此类临床表现的产生机制缺乏系统深入的研究。该文建立了慢性温和不可预见性应激(chronic mild unpredictable stimulation,CUMS)抑郁症大鼠模型。在诱导抑郁症模型大鼠过程中通过外源补充白兰氏鸡精(Brand’s essence of chicken,BEC),应用ELISA、荧光定量PCR等方法从生理水平、基因转录水平研究BEC对生物钟系统的影响以及是否具有减轻抑郁症症状的作用。研究结果表明,BEC能有效调控和稳定生物钟母钟[下丘脑视交叉上核(suprachiasmatic nucleus,SCN)]及子钟(肝脏、脂肪组织)中生物钟基因的表达时相,减缓由CUMS引起的探索行为活动下降以及血清中相关激素的分泌紊乱,从而减轻抑郁症相关症状及有效预防抑郁症的发生。     

BDNF或5HTTLPR与抑郁症的研究

抑郁症是以抑郁为主要临床表征的一种精神疾病,近年抑郁症发病率正呈逐年上升趋势,如不加以干预,对患者及患者家庭、社会都会产生重大影响.对于抑郁症发病机制目前尚无定论,现有研究均停留在假说阶段.众多假说中脑源性神经营养因子(BDNF)和5-羟色胺转运体基因连锁多肽性区域(5-HTTLPR)参与抑郁症的病理生理过程,分别发挥重要作用,其基因也是抑郁症的候选基因,本研究对BDNF、5-HTTLPR在抑郁症及抗抑郁治疗等方面的作用进行文献综述.     

加压素和催产素在中枢神经系统中的作用

加压素(AVP)和催产素(OT)是密切相关的2种肽,它们的基因均位于人类第20条染色体上。来自于神经垂体分泌的AVP和OT直接释放到循环系统,调节靶细胞的活动:来自于中枢轴突末梢释放AVP和OT遍布整个中枢神经系统,作为神经递质或调制调节神经细胞的活动,在特定脑区与记忆及精神上的疾病有关。研究AVP和OT在中枢神经系统中的作用,不仅有助于揭示精神分裂症、抑郁、酗酒、老年性痴呆、帕金森氏病等的致病机理,而且对揭示人类社会婚配制度的神经生物学机制提供参考资料。     

体育运动对抑郁症的干预研究

抑郁症(depression)是一种十分普遍的神经精神疾病,它是先天遗传因素和后天环境因素共同作用的结果,并有其复杂的神经生理和病理机制。抑郁症患者的健康水平和生存质量普遍较低,严重抑郁患者还会有自杀的倾向。目前,药物疗法依然是抑郁症治疗的主要手段,但是长期服药不仅会带来严重的副作用,还会加重患者经济负担,降低治疗依从性。本研究在综述抑郁症的各种诱发因素的基础上,重点探讨了体育运动对抑郁症的干预作用,以及运动干预抑郁症的相关机制,同时还归纳了针对抑郁症的运动干预方案,以期为抑郁症的预防与治疗提供可供参考的方法。     

光疗及光照剂量对抑郁症的作用研究进展

抑郁症是一种患病率高、易复发、自杀率高的精神障碍疾病,容易导致认知功能损伤等问题.光疗以无创、副作用小、疗效快等优势受到广泛的关注,为调节抑郁症生物节律和睡眠障碍等症状提供了新的可能性.光信号通过视网膜神经节细胞投射到抑郁脑区参与非视觉成像功能,激活神经细胞活动,分泌神经递质使神经通路产生生理性改变,对生物机体的昼夜节...     

成纤维细胞生长因子9在抑郁症及其运动干预调节中的作用

成纤维细胞生长因子9（fibroblast growth factor 9, FGF9）是成纤维细胞生长因子（fibroblast growth factor,FGF）家族成员之一,属于一种自分泌或旁分泌生长因子。在脑组织中,FGF9主要表达于海马和皮质区,具有促进细胞增殖和维持细胞存活的功能。研究发现,FGF家族在抑郁症患者的多个脑区出现表达紊乱,FGF9在抑郁行为中扮演着负调控角色,但其介导抑郁行为的分子机制尚不清楚。本文综述了FGF9及其家族成员在抑郁中的作用; 围绕其受体（FGFR）信号在中枢神经系统中的功能特点,深入分析FGF9调节抑郁行为中的作用机制;结合运动抗抑郁的神经营养假说,提出经由FGFR/GSK3β/β-catenin通路的FGF信号,可能介导抑郁症的运动干预机制的假设。这些将为FGF9介导抑郁行为和运动抗抑郁的有关研究提供理论的基础和探索的思路。     

SIRT1基因在抑郁症中的作用及机制研究进展

抑郁症是一类高致残率且难治愈的精神类疾病,目前其临床诊断和治疗都面临很大的困难,因此研究抑郁症患病机制,寻找抑郁症的潜在治疗靶点,并开发有效临床治疗手段刻不容缓。沉默信息调节因子2同源体1 (silent mating type information regulator 2 homolog 1, SIRT1)作为一种去乙酰化酶,参与细胞衰老、癌症、心血管疾病等多种生物学过程。近年来,越来越多的研究发现SIRT1基因在抑郁症发病过程中发挥了重要的作用,但是其机制尚不明确。本文主要总结了海马、前额叶皮层、杏仁核、下丘脑视交叉上核脑区和伏隔核中SIRT1基因影响抑郁症病理过程的相关研究进展,以期为抑郁症机制研究和抗抑郁药物的研发提供一定的参考和帮助。     

神经发生在抑郁症发生发展中的作用

抑郁症是一种常见的精神疾病。全球范围内,预计有3.5亿人患有抑郁症,重度抑郁症已成为世界范围内致残的第二大疾病,并给家庭和社会带来严重的经济负担。尽管最近在神经科学研究方面取得了很大进展,但抑郁症病理生理学基础上的神经生物学机制仍知之甚少。神经发生是新的神经元产生的过程,神经发生除维持正常的生理功能外,近几十年来研究发现,神经发生在抑郁症的病理生理学和症状学中起着重要作用。深入研究神经发生的调控机制,不仅可以阐明神经发生在抑郁症病因学中的作用,同时对理解治疗药物的药理学机制以及发现新药具有重要意义。因此,该综述对神经发生在抑郁症的作用及机制进行了讨论。     

Spinal proerectile effect of oxytocin in anesthetized rats

The spinal cord contains the neural network that controls penile erection. This network is activated by information from peripheral and supraspinal origin. We tested the hypothesis that oxytocin (OT), released at the lumbosacral spinal cord level by descending projections from the paraventricular nucleus, regulated penile erection. In anesthetized male rats, blood pressure and intracavernous pressure (ICP) were monitored. Intrathecal (it) injection of cumulative doses of OT and the selective OT agonist [Thr(4),Gly(7)]OT at the lumbosacral level elicited ICP rises whose number, amplitude, and area were dose dependent. Thirty nanograms of OT and one-hundred nanograms of the agonist displayed the greatest proerectile effects. Single injections of OT also elicited ICP rises. Preliminary injection of a specific OT-receptor antagonist, hexamethonium, or bilateral pelvic nerve section impaired the effects of OT injected it. NaCl and vasopressin injected it at the lumbosacral level and OT injected it at the thoracolumbar level or intravenously had no effect on ICP. The results demonstrate that OT, acting at the lumbosacral spinal cord, elicits ICP rises in anesthetized rats. They suggest that OT, released on physiological activation of the PVN in a sexually relevant context, is a potent activator of spinal proerectile neurons.     

Oxytocin and social affiliation in humans

A conceptual model detailing the process of bio-behavioral synchrony between the online physiological and behavioral responses of attachment partners during social contact is presented as a theoretical and empirical framework for the study of affiliative bonds. Guided by an ethological behavior-based approach, we suggest that micro-level social behaviors in the gaze, vocal, affective, and touch modalities are dynamically integrated with online physiological processes and hormonal response to create dyad-specific affiliations. Studies across multiple attachments throughout life are presented and demonstrate that the extended oxytocin (OT) system provides the neurohormonal substrate for parental, romantic, and filial attachment in humans; that the three prototypes of affiliation are expressed in similar constellations of social behavior; and that OT is stable over time within individuals, is mutually-influencing among partners, and that mechanisms of cross-generation and inter-couple transmission relate to coordinated social behavior. Research showing links between peripheral and genetic markers of OT with concurrent parenting and memories of parental care; between administration of OT to parent and infant's physiological readiness for social engagement; and between neuropeptides and the online synchrony of maternal and paternal brain response in social-cognitive and empathy networks support the hypothesis that human attachment develops within the matrix of biological attunement and close behavioral synchrony. The findings have conceptual implications for the study of inter-subjectivity as well as translational implications for the treatment of social disorders originating in early childhood, such as autism spectrum disorders, or those associated with disruptions to early bonding, such as postpartum depression or child abuse and neglect. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.     

Enhanced corticosterone concentrations and attenuated Fos expression in the medial amygdala of female oxytocin knockout mice exposed to psychogenic stress

Centrally released oxytocin (OT) is believed to attenuate the response of the hypothalamic-pituitary-adrenal (HPA) axis to psychogenic stress. To test this hypothesis, we measured plasma corticosterone concentrations and Fos-immunoreactive protein in the paraventricular nucleus of the hypothalamus (PVN) and limbic brain areas of female wild-type and OT knockout mice that were exposed to a shaker platform, a predominantly psychogenic stress. Plasma corticosterone concentrations after shaker stress were higher in female OT knockout mice than wild-type mice. Genotypic differences in the corticosterone response after shaker stress persisted across all stages of the estrous cycle and when mice were conditioned to repeated shaker stress. Shaker stress activated Fos in OT-positive neurons of wild-type mice and corticotropin-releasing hormone-positive, but not vasopressin-positive, neurons within the PVN of wild-type and OT knockout mice. Fos expression was also increased after shaker stress in the bed nucleus of the stria terminalis, medial and central nuclei of the amygdala, medial preoptic area, and the paraventricular nucleus of the thalamus of wild-type and OT knockout mice. However, Fos expression in the medial amygdala was significantly lower in female OT knockout mice than wild-type mice. Our findings indicate heightened stress-induced corticosterone release in female OT knockout mice. Therefore, the results suggest that OT pathways play a role in attenuating the HPA axis response to psychogenic stress in female mice.     

Demonstration of a different localization of perikarya immunoreactive to oxytocin and vasopressin in the cat hypothalamus

Using immunohistochemical techniques, we demonstrated oxytocin (OT) and vasopressin (AVP) neurons in the cat hypothalamus. The OT immunoreactive neurons were found mainly in the paraventricular nucleus, supraoptic nucleus and dorsal accessory group located lateral to the fornix. In addition to these hypothalamic structures, the AVP immunoreactive neurons were observed in the suprachiasmatic nucleus, ventral accessory group located in the retrochiasmatic area and lateral accessory group, dorsal to the supraoptic nucleus caudally, and ventral to the medial part of the internal capsule rostrally. We further demonstrated a different localization of the OT and AVP immunoreactive neurons in the paraventricular and supraoptic nuclei.     

Urinary oxytocin as a noninvasive biomarker of positive emotion in dogs

A reliable assay based on physiological parameters that does not require subjective input from the owners is required to assess positive emotions in dogs. In addition, when viewed from an animal welfare perspective, physiological parameters should be collected in a noninvasive manner. Oxytocin (OT) is a biomarker that may be associated with a calm, relaxed state, and positive emotion. We measured the time-lapse in the concentration of plasma OT relative to urinary OT using a radioimmunoassay with sufficient sensitivity and low variability, and examined the relationship between OT and cortisol. Six dogs were injected with exogenous OT intravenously to increase the blood OT concentration. As a result, the highest concentration of urinary OT occurred 1 h after the injection, although there was little change in urinary cortisol. Moreover, to evaluate the influence of stimuli on urinary OT and cortisol, we provided three stimuli of eating food, exercising and stroking, all of which were assumed to inspire a positive emotion in dogs, and significantly increased urinary OT concentrations. Our findings indicate that urinary OT might be useful as a noninvasive and objective biomarker of positive emotion in dogs.     

Variations in concentration of oxytocin and vasopressin in the paraventricular nucleus of the hypothalamus during the estrous cycle in rats

Oxytocin (OT) and arginine-8-vasopressin (AVP) were measured by radioimmunoassay in micropunched hypothalamic neurosecretory nuclei of estrous cycling female Sprague-Dawley rats. In the paraventricular nucleus (PVN): the concentration (pg/microgram protein) of OT was significantly higher in rats in diestrus than during proestrus, estrus, or metestrus, while the concentration during metestrus was significantly greater than in proestrus and estrus; the concentration of AVP was significantly lower in animals in estrus than during the other three stages; because the paraventricular OT levels dropped before proestrus, the AVP/OT ratio was significantly greater in animals in proestrus than in diestrus, metestrus, and estrus. In the supraoptic nucleus (SON) a similar trend was noted: the concentration of OT was highest during diestrus, and AVP was lowest during estrus, though neither was significantly different from other stages. Because the OT and AVP cycles in the SON were asynchronous, the ratio of AVP to OT was significantly higher in proestrus than in metestrus or diestrus and significantly greater in estrus than during diestrus. In contrast to these two areas, peptide concentrations did not vary significantly across the estrous cycle in other sites of nonapeptide synthesis, i.e. the anterior commissural nucleus (ACN) and the suprachiasmatic nuclei (SCN).     

Roles of oxytocin in spatial learning and memory in the nucleus basalis of Meynert in rats

The present study was performed to explore the role of oxytocin (OT) in spatial learning and memory in the nucleus basalis of Meynert (NBM) of rats. The latency, distance and swimming path to find the platform were tested by Morris water maze and recorded by a video camera connected to a computer. Intra-NBM injections of 2 or 10 nmol of OT, but not 0.2 nmol of OT, induced significant increase on the latency of spatial learning. Rats receiving intra-NBM administrations of 2 or 10 nmol of OT showed a more random search pattern. There were no significant changes in the swimming speed in Morris water maze test after the injection of OT. Furthermore, the impaired effect of OT on the latency of spatial learning was blocked by intra-NBM injection of the selective OT antagonist Atosiban, indicating that the effect of OT was mediated by OT receptor in the NBM of rats. Moreover, there were no influences of OT or Atosiban on the retention performance in rats. The results suggest that OT plays an inhibitory role in spatial learning in the NBM; the effect is mediated by OT receptor.     

Subcaste differences in neural activation suggest a prosocial role for oxytocin in eusocial naked mole-rats

The neuropeptide oxytocin (OT) influences prosocial behavior(s), aggression, and stress responsiveness, and these diverse effects are regulated in a species- and context-specific manner. The naked mole-rat (Heterocephalus glaber) is a unique species with which to study context-dependent effects of OT, exhibiting a strict social hierarchy with behavioral specialization within the subordinate caste: soldiers are aggressive and defend colonies against unfamiliar conspecifics while workers are prosocial and contribute to in-colony behaviors such as pup care. To determine if OT is involved in subcaste-specific behaviors, we compared behavioral responses between workers and soldiers of both sexes during a modified resident/intruder paradigm, and quantified activation of OT neurons in the hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON) using the immediate-early-gene marker c-fos co-localized with OT neurons. Resident workers and soldiers were age-matched with unfamiliar worker stimulus animals as intruders, and encounters were videorecorded and scored for aggressive behaviors. Colony-matched controls were left in their home colony for the duration of the encounters. Brains were extracted and cell counts were conducted for OT immunoreactive (ir), c-fos-ir, and percentage of OT-c-fos double-labeled cells. Results indicate that resident workers were less aggressive but showed greater OT neural activity than soldiers. Furthermore, a linear model including social treatment, cortisol, and subcaste revealed that subcaste was the only significant predictor of OT-c-fos double-labeled cells in the PVN. These data suggest that in naked mole-rats OT promotes prosocial behaviors rather than aggression and that even within subordinates status exerts robust effects on brain and behavior.     

Oxytocinergic and serotonergic systems involvement in sodium intake regulation: satiety or hypertonicity markers?

Previous studies demonstrated the inhibitory participation of serotonergic (5-HT) and oxytocinergic (OT) neurons on sodium appetite induced by peritoneal dialysis (PD) in rats. The activity of 5-HT neurons increases after PD-induced 2% NaCl intake and decreases after sodium depletion; however, the activity of the OT neurons appears only after PD-induced 2% NaCl intake. To discriminate whether the differential activations of the 5-HT and OT neurons in this model are a consequence of the sodium satiation process or are the result of stimulation caused by the entry to the body of a hypertonic sodium solution during sodium access, we analyzed the number of Fos-5-HT- and Fos-OT-immunoreactive neurons in the dorsal raphe nucleus and the paraventricular nucleus of the hypothalamus-supraoptic nucleus, respectively, after isotonic vs. hypertonic NaCl intake induced by PD. We also studied the OT plasma levels after PD-induced isotonic or hypertonic NaCl intake. Sodium intake induced by PD significantly increased the number of Fos-5-HT cells, independently of the concentration of NaCl consumed. In contrast, the number of Fos-OT neurons increased after hypertonic NaCl intake, in both depleted and non-depleted animals. The OT plasma levels significantly increased only in the PD-induced 2% NaCl intake group in relation to others, showing a synergic effect of both factors. In summary, 5-HT neurons were activated after body sodium status was reestablished, suggesting that this system is activated under conditions of satiety. In terms of the OT system, both OT neural activity and OT plasma levels were increased by the entry of hypertonic NaCl solution during sodium consumption, suggesting that this system is involved in the processing of hyperosmotic signals.