表观遗传修饰在学习记忆中的研究进展

学习记忆是大脑的重要功能.记忆的形成涉及基因转录、新蛋白质合成和突触可塑性改变等一系列分子和细胞乃至神经环路的变化.近些年研究者逐渐发现各种表观遗传修饰,包括DNA甲基化、组蛋白修饰及RNA修饰在各种学习记忆类型、记忆阶段和突触可塑性中发挥了不同程度的作用.本文阐述了参与学习记忆的不同表观遗传调控因子,为进一步理解学习...     

神经元的突触可塑性与学习和记忆

大量研究表明,神经元的突触可塑性包括功能可塑性和结构可塑性,与学习和记忆密切相关.最近,在经过训练的动物海马区,记录到了学习诱导的长时程增强(long term potentiation,LTP),如果用激酶抑制剂阻断晚期LTP,就会使大鼠丧失训练形成的记忆.这些结果指出,LTP可能是形成记忆的分子基础.因此,进一步研究哺乳动物脑内突触可塑性的分子机制,对揭示学习和记忆的神经基础有重要意义.此外,在精神迟滞性疾病和神经退行性疾病患者脑内记录到异常的LTP,并发现神经元的树突棘数量减少,形态上产生畸变或萎缩,同时发现,产生突变的基因大多编码调节突触可塑性的信号通路蛋白,故突触可塑性研究也将促进精神和神经疾病的预防和治疗.综述了突触可塑性研究的最新进展,并展望了其发展前景.     

突触蛋白在学习记忆过程中的作用

学习和记忆是脑的高级功能。学习指人和动物获得外界知识的神经过程;记忆指将获得的知识储存和读出的神经过程。突触蛋白(synapsin)是一种与突触结构和功能密切相关的膜蛋白,在突触的可塑性以及长时程增强(long-timepotentiation,LTP)中起着重要作用。而突触可塑性是突触对内外环境变化作出反应的能力,是学习记忆的神经生物学基础。LTP一直被认为是学习记忆的神经基础之一,是突触可塑性的功能指标,也是研究学习记忆的理想模型。该文介绍突触蛋白在学习记忆过程中的作用及机制、突触蛋白在学习记忆研究中的应用。     

药物成瘾相关的神经结构可塑性改变

不计后果的药物渴求和滥用是药物成瘾的一个显著特征。药物滥用可以诱导行为学和心理学持续性改变的发生,这些持续性改变由相关神经通路(尤其是奖赏系统)神经结构的可塑性变化所引起。本文综述了安非他明、可卡因、尼古丁和吗啡等药物诱发的相关脑区的神经可塑性改变以及引起这些改变的可能原因。药物成瘾诱发的神经结构可塑性改变反映了相关神经系统突触连接的重塑,这些重塑改变该系统的功能,由此便产生了药物滥用的一系列后遗症状———包括成瘾。     

谷氨酸受体调控树突棘形态可塑性的研究进展

树突棘是神经元之间产生直接联系的部位,其形态可塑性是记忆的结构基础。谷氨酸信息传递是中枢神经信息传递的主要方式,能产生突触传递效率的可塑性,由此引起树突棘形态的可塑性变化。本文从谷氨酸受体途径的角度对树突棘形态可塑性的调控机制做一综述。谷氨酸受体主要通过其下游信号分子调节棘内肌动蛋白动力学蛋白,参与树突棘的形态发生和稳定。该作用在局部受到不同的蛋白、信号分子、激素、mi RNAs的调节,从而参与生理及病理过程。最后,提出展望,研究脑区特异的局部微环境变化对记忆相关疾病病因及治疗探讨有参考价值。     

多巴胺调节海马神经元可塑性的研究进展

多巴胺是脑内重要的信息传递物质,不仅可以作为递质释放到前额叶、伏隔核等脑区,直接进行信息传递,也可以作为调质调节其它突触递质的传递,并影响神经元可塑性。海马参与构成边缘系统,受多巴胺能神经支配,执行着有关学习记忆以及空间定位的功能。海马神经元的可塑性是学习记忆的细胞分子基础。研究表明,多巴胺对海马神经元的突触可塑性和兴奋性可塑性都具有重要的调节作用。本文扼要综述多巴胺对海马神经元突触可塑性和兴奋性可塑性的调节机制的研究进展,以期为DA系统参与海马区学习记忆功能的研究提供新思路,更深入地了解学习记忆的神经机制。     

脑内ATF4对学习记忆的调节作用

转录激活因子4(ATF4)属于碱性亮氨酸拉链结构域蛋白中的ATF/CREB转录因子家族,ATF4在脑内广泛表达,在应激、痛觉、突触可塑性和神经退行性变等中发挥重要作用。学习与记忆是脑的高级功能之一,学习是获取新信息的过程,记忆是将信息进行编码、储存及提取的过程,二者被认为是认知活动的基础。突触可塑性是突触在形态、结构和功能上的可变性和可修饰性,与神经系统的发育和学习记忆等脑的高级功能密切相关。突触可塑性的长时程增强和长时程抑制是学习和记忆形成的基础。近年来研究发现, ATF4与突触可塑性和学习记忆密切相关,其在神经退行性变、脑损伤和药物成瘾等疾病中扮演重要角色,有必要深入理解ATF4在学习记忆障碍相关疾病中发挥的作用,为相关疾病的治疗提供新靶点。     

果蝇记忆相关蛋白的合成受RNA诱导沉默复合物通路的调节

蛋白质的合成是脊椎动物和无脊椎动物长时程记忆形成的普遍特征,同时伴随着细胞水平的一系列变化,包括突触和神经环路功能的可塑性改变。在突触部位合成的蛋白可能是突触和神经环路可塑性的基础,但在长时程记忆建立过程中突触蛋白的合成模式及其调节因子尚不清楚。钙一钙调蛋白依赖激酶Ⅱ（calcium／calmodulin-dependent kinaseⅡ,CaMKⅡ）在突触部位合成,是记忆形成所必需的蛋白。     

代谢型谷氨酸受体在突触可塑性中的作用

突触可塑性是近几年神经科学研究的热点之一,因为它对于理解神经系统的学习、学习和记忆、多咱神经疾病等许多过程有着重要的意义。除了离子型谷氨酸受体外,代谢型谷氨酸受体也参与了一些脑区中不同形式的突触可塑性变化。本文就代谢型谷氨酸受体选择性激动剂和拮抗剂对长时程增强和长时程抑制的作用进行了综述,以助于人们进一步理解突触可塑性的细胞和分子机制。     

神经细胞粘附分子与记忆

记忆的形成阶段包含着神经元突触的可塑性变化过程.近年来的研究表明,神经细胞粘附分子可同时增进突触的可塑性和维持突触结构的稳定性.许多研究证实神经细胞粘附分子对与学习和记忆相关的过程起着一定的调节作用.     

Role for dopamine in malonate-induced damage in vivo in striatum and in vitro in mesencephalic cultures

Defects in mitochondrial energy metabolism have been implicated in the pathology of several neurodegenerative disorders. In addition, the reactive metabolites generated from the metabolism and oxidation of the neurotransmitter dopamine (DA) are thought to contribute to the damage to neurons of the basal ganglia. We have previously demonstrated that infusions of the metabolic inhibitor malonate into the striata of mice or rats produce degeneration of DA nerve terminals. In the present studies, we demonstrate that an intrastriatal infusion of malonate induces a substantial increase in DA efflux in awake, behaving mice as measured by in vivo microdialysis. Furthermore, pretreatment of mice with tetrabenazine (TBZ) or the TBZ analogue Ro 4-1284 (Ro-4), compounds that reversibly inhibit the vesicular storage of DA, attenuates the malonate-induced DA efflux as well as the damage to DA nerve terminals. Consistent with these findings, the damage to both DA and GABA neurons in mesencephalic cultures by malonate exposure was attenuated by pretreatment with TBZ or Ro-4. Treatment with these compounds did not affect the formation of free radicals or the inhibition of oxidative phosphorylation resulting from malonate exposure alone. Our data suggest that DA plays an important role in the neurotoxicity produced by malonate. These findings provide direct evidence that inhibition of succinate dehydrogenase causes an increase in extracellular DA levels and indicate that bioenergetic defects may contribute to the pathogenesis of chronic neurodegenerative diseases through a mechanism involving DA.     

Scurvy in capybaras bred in captivity in Argentine

In order to determine if the absence of vitamin C in the diet of capybaras (Hydrochoerus hydrochaeris) causes scurvy, a group of seven young individuals were fed food pellets without ascorbic acid, while another group of eight individuals received the same food with 1 g of ascorbic acid per animal per day. Animals in the first group developed signs of scurvy-like gingivitis, breaking of the incisors and death of one animal. Clinical signs appeared between 25 and 104 days from the beginning of the trial in all individuals. Growth rates of individuals deprived of vitamin C was considerably less than those observed in the control group. Deficiency of ascorbic acid had a severe effect on reproduction of another population of captive capybaras. We found that the decrease in ascorbic acid content in the diet affected pregnancy, especially during the first stages. The results obtained suggest that it is necessary to supply a suitable quantity of vitamin C in the diet of this species in captivity.     

Changes in lactate dehydrogenase activity in chicken tissues in hyperthyreosis in ontogenesis

The lactate dehydrogenase activity in reactions of lactate oxidation and synthesis was studied in subfractions of the chicken brain, heart and liver at the embryonal, early postembryonal and adult stages of development after thyroxine administration. It has been shown that during embryogenesis thyroxine predominantly enhanced the rate of lactate oxidation in the mitochondrial tissues. A marked increase in the lactate synthesis was found in cytoplasm of the adult chicken tissues. Specificity of enzyme activity alterations was detected in the chicken brain during ontogenesis after thyroxine administration.     

SSTR5 ablation in islet results in alterations in glucose homeostasis in mice

Somatostatin (SST) peptide is a potent inhibitor of insulin secretion and its effect is mediated via somatostatin receptor 5 (SSTR5) in the endocrine pancreas. To investigate the consequences of gene ablation of SSTR5 in the mouse pancreas, we have generated a mouse model in which the SSTR5 gene was specifically knocked down in the pancreatic beta cells (betaSSTR5Kd) using the Cre-lox system. Immunohistochemistry analysis showed that SSTR5 gene expression was absent in beta cells at three months of age. At the time of gene ablation, betaSSTR5Kd mice demonstrated glucose intolerance with lack of insulin response and significantly reduced serum insulin levels. Insulin tolerance test demonstrated a significant increase of insulin clearance in vivo at the same age. In vitro studies demonstrated an absence of response to SST-28 stimulation in the betaSSTR5Kd mouse islet, which was associated with a significantly reduced SST expression level in betaSSTR5Kd mice pancreata. In addition, betaSSTR5Kd mice had significantly reduced serum glucose levels and increased serum insulin levels at 12 months of age. Glucose tolerance test at an older age also indicated a persistently higher insulin level in betaSSTR5Kd mice. Further studies of betaSSTR5Kd mice had revealed elevated serum C-peptide levels at both 3 and 12 months of age, suggesting that these mice are capable of producing and releasing insulin to the periphery. These results support the hypothesis that SSTR5 plays a pivotal role in the regulation of insulin secretion in the mouse pancreas.