抑郁症患者视觉损伤的研究进展

视觉损伤在抑郁症患者中较为常见，抑郁症患者的视觉处理能力在各个阶段都受到了损害，目前研究集中在对比敏感度、视觉掩蔽、视觉注意、面部表情识别、运动视觉等方面。视觉加工障碍会导致正常感知觉的缺陷，因此无法正常激活奖赏通路，进而加重抑郁症患者的快感缺乏。文章就抑郁症视觉加工方面的损害情况及相关的脑机制进行综述，旨在为进一步的研究作参考。     

神经营养素在视觉中枢发育中的作用

神经营养素在发育的视觉系统中表达,并且能够以活动依赖的方式调节突触可塑性及神经元生长,在视觉系统发育中起重要作用.     

1000/人工视觉假体视觉映像信息处理模型

视觉映像的信息处理机制是人工视觉研究中最重要的基础工作和核心技术之一。本文在阐述人类视觉信息获取及处理原理的基础上,提出一种人工视觉映像信息处理模型。然后详细阐述这一模型在学习训练阶段和应用阶段的系统结构和关键技术。     

鞍区肿瘤的显微手术治疗中视觉功能保护

目的 探讨鞍区肿瘤患者视觉功能障碍的原因和手术切除过程中视觉功能的保护.方法 回顾性分析2001年1月至2010年10月手术治疗的74例鞍区肿瘤患者临床资料,包括手术入路及手术前后视觉功能状况等.结果 术后随访3月至2年,术前视觉功能正常的25例患者中,术后没有发现视觉功能下降;术前视觉功能障碍的49例患者中,术后视觉...     

神经营养在视觉中枢发育中的作用

神经营养素在发育的视觉系统中表达，并且能够以活动依赖的方式调节突触可塑性及神经元生长，在视觉系统发育中起重要作用。     

应用视觉诱发电位术中监测视觉功能的研究

目的评价视觉诱发电位(VEP)在切除累及视路病灶的手术中监护视觉功能方面的可行性和可靠性。方法回顾分析31例累及视路病变的患者的临床资料,全静脉麻醉后手术,用2.1Hz的闪光二极管刺激患者,通过头皮(29例)或皮层(2例)记录视觉诱发电位,分析术中诱发电位的变化与术后视觉功能变化的关系。结果 25例患者描记出清晰、可重复的波形;VEP异常或消失的患者有7例,术后视力下降2例,视野缺损加重6例;8例术中出现VEP波形的异常,予及时改变手术策略,避免对视路的进一步骚扰后,2min内波形渐趋正常,术后仅有1例出现视野缺损。结论视觉诱发电位是一种能够提供实时视觉功能监测的可靠方法,能及时发现视路损伤。     

视觉诱发电位在颅内肿瘤诊治中的应用

视觉诱发电位（Visual evoked potentials,VEP）通过监测视觉通路的生物电变化,已被广泛应用于临床评价神经系统及眼科系统病变的视觉功能状态。颅内脑肿瘤常通过直接侵袭或压迫视觉通路神经纤维,造成视觉传导功能的损害。VEP技术主要应用于评价颅内脑肿瘤的视觉功能状态,对脑肿瘤的早期筛选,鉴别视路不同部位肿瘤的位置,脑肿瘤的动态观察及脑肿瘤手术中监护等方面。     

中西方纯失读症在视觉词形加工机制上的差异

纯失读症是损害定位于阅读早期阶段即词形加工的功能障碍,症状单一且病变部位特殊,多累及视觉词形加工区域。文字阅读作为一种获得性高级神经功能,与文化密切相关,故比较中西方纯失读症的异同能够更加深入地了解视觉词形加工机制。中西方纯失读症具有不同临床表现,文字信号特征的差异性是根本原因,视觉词形加工区域的可塑性是神经生物学基础。中西方文字阅读均呈现左侧半球偏侧化特点,但汉语纯失读症的特殊现象可推测右侧大脑半球在汉语加工中的作用更为突出。中西方阅读的fMRI研究均提示视觉词形加工区域内部存在等级结构,对应于亚词汇加工的分级制度,但尚不足以解释汉语纯失读症中词长效应阙如等现象。汉字辨认可能更依赖于腹侧视觉通路即整字的加工。     

前额叶损伤患者的视-空间工作记忆改变

目的 探讨前额叶不同亚区损伤患者的视-空间工作记忆障碍.方法 将20例前额叶不同亚区损伤患者以及20名与其人口学资料相匹配的健康人作为被试,采用视觉面孔和视觉空间的延迟匹配任务对上述2组进行视-空间工作记忆测试.结果 与健康对照组(72.9%±6.1%)相比,前额叶腹侧(ventral prefrontal cortex,VPFC)损伤的患者视觉客体工作记忆的正确率(46.4%±11.4%)明显下降,差异有统计学意义(U=1.00,P<0.01);而前额叶背外侧(dorsolateral prefrontal cortex,DLPFC)损伤的患者在视觉客体(50.4%±15.1%)和视觉空间(72.6%±18.6%)工作记忆均有明显损伤,与对照组(72.9%±6.1%、89.4%±10.1%)比较差异均有统计学意义(U=-20.5、59.5,均P<0.01).对左、右前额叶损伤的2组患者进行分析,结果表明2组患者在视觉客体和空间工作记忆正确率的比较差异均无统计学意义.对前额叶亚区进行左右侧比较,2组VPFC患者在视觉客体和视觉空间工作记忆差异均无统计学意义;左侧DLPFC损伤组和右侧DLPFC损伤组在视觉客体工作记忆正确率和视觉面孔工作记忆正确率方面,差异均无统计学意义.结论 前额叶是工作记忆加工的重要脑区,其不仅参与了视觉客体的工作记忆加工过程,同时参与了视觉空间的工作记忆加工,而且对于前额叶不同亚区在视-空间工作记忆加工过程中还存在分离.     

光学相干断层成像术在中枢神经系统脱髓鞘疾病中的应用价值

光学相干断层成像术(optical coherence tomography,OCT)可客观清楚地显示视网膜结构变化,在眼科疾病诊疗中被广泛应用.视神经炎(optic neuritis,ON)是中枢神经系统脱髓鞘疾病的主要临床表现,可引起不同程度的视觉功能障碍.在临床工作中对视觉功能的评估方法 多样,各有利弊.现就OC...     

The role of neurotrophins in axonal growth, guidance, and regeneration

Neurotrophins are proteins that regulate neuronal survival, axonal growth, synaptic plasticity and neurotransmission. They are members of the neurotrophic factors family and include factors such as the nerve growth factor (NGF), the brain derived neurotrophic factor (BDNF), the neurotrophin-3 (NT-3), and the neurotrophin-4/5 (NT-4/5). These molecules bind to two types of receptors: i) tyrosine kinase receptors (TrkA, TrkB, TrkC) and ii) a common neurotrophin receptor (p75NTR). The two receptor types can either suppress or enhance each other's actions. Neurotrophins have a multifunctional role both in the central and peripheral nervous system. They have been suggested as axonal guidance molecules during the growth and regeneration of nerves. It has also been proven that they stimulate axonal growth by mediating the polymerization and accumulation of F-actin in growth cones and axon shafts. Neurotrophins, as other neurotrophic factors, have been shown that they reduce neuronal injury by exposure to excitotoxins, glucose deprivation, or ischemia. Furthermore, the nerve regeneration promoting effect of these growth factors is well documented for many different models of central or peripheral nervous system injury. Several studies have shown that exogenous administration of these factors has protective properties for injured neurons and stimulates axonal regeneration. Based on these properties, these molecules may be used as therapeutic agents for treating degenerative diseases and traumatic injuries of both the central and peripheral nervous system.     

Effects of dark rearing on phosphorylation of neurotrophin Trk receptors

Total lack of visual experience (dark rearing, DR) is known to affect development of mammalian visual cortex (VC) and to prolong the critical period of visual cortical plasticity. Neurotrophins (NTs) have been proposed to play a relevant role in activity dependent processes important for the final shaping of cortical visual connections. Neurotrophin supply or antagonism of endogenous NT action profoundly affect visual cortical development and plasticity; in particular, exogenous supply of NTs counteracts DR effects on VC development. However, the effects of DR on NT expression are still debated and mounting evidence reports a mismatch between BDNF mRNA and protein expression in DR animals. To gain insight into the effects of DR on expression of nerve growth factor (NGF) and the functional state of NT signalling pathways, we assessed the phosphorylation state of Trk receptors in light-reared animals (LR), in dark-reared animals (DR), in DR animals briefly exposed to light and in DR animals with exogenous supply of NTs [NGF, brain-derived neurotrophic factor (BDNF) and NT-4] in the VC. We report that DR increases the expression of NGF but reduces the phosphorylation of TrkA and TrkB receptors with respect to LR; normal phosphorylation is rapidly rescued by a brief exposure to light. Exogenous supply of NGF, BDNF or NT4 in DR animals also rescues the phosphorylation of their receptors.     

Role of neurotrophins in pregnancy and offspring brain development

Neurotrophins are a family of functionally and structurally related proteins which play a key role in the survival, development, and function of neurons in both the central and peripheral nervous systems. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) are the family members of neurotrophins. Neurotrophins play a crucial role in influencing the development of the brain and learning and memory processes. Studies demonstrate that they also play crucial role in influencing reproductive and immune systems. Neurotrophins have been shown to influence various processes in the mother, placenta, and fetus during pregnancy. Development and maturation of feto-placental unit and the fetal growth trajectories are influenced by neurotrophins.In addition to neurotrophins, neuropeptides like neuropeptide Y also play a crucial role during various processes of pregnancy and during fetal brain development. Neurotrophins have also been shown to have a cross talk with various angiogenic factors and influence placental development. Alterations in the levels of neurotrophins and neuropeptides lead to placental pathologies resulting in various pregnancy complications like preeclampsia, intrauterine growth restriction and preterm births. Studies in animals have reported low levels of maternal micronutrients like folic acid, vitamin B₁₂ and omega-3 fatty acids influence brain neurotrophins resulting in impaired cognitive functioning in the offspring. Maternal nutrition is also known to affect the expression of neuropeptides. It is essential to understand the role of various neurotrophins across various stages of pregnancy and its relationship with neurodevelopmental outcomes in children. This will lead to early prediction of poor neurodevelopmental outcomes. The present review describes evidence describing the role of neurotrophins in determining pregnancy outcome and altered neurodevelopment in the offspring. The possible mechanism through which maternal nutrition influences neurotrophins and neuropeptides to regulate offspring brain development and function is also discussed.     

Physiology of BDNF: focus on hypothalamic function

Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family which interacts with high-affinity protein kinase receptors (Trk) and the unselective p75(NGFR) receptor. The BDNF gene has a complex structure with multiple regulatory elements and four promoters that are differentially expressed in central or peripheral tissue. BDNF expression is regulated by neuronal activity or peripheral hormones. Neurotrophins regulate the survival and differentiation of neurons during development but growing evidence indicates that they are also involved in several functions in adulthood, including plasticity processes. BDNF expression in the central nervous system (CNS) is modified by various kinds of brain insult (stress, ischemia, seizure activity, hypoglycemia, etc.) and alterations in its expression may contribute to some pathologies such as depression, epilepsy, Alzheimer's, and Parkinson's disease. Apart from very traumatic situations, the brain functioning is resilient to stress and capable of adaptive plasticity. Neurotrophins might act as plasticity mediators enhancing this trait which seems to be crucial in adaptive processes. In addition to documenting all of the topics mentioned above in the CNS, we review the state of the art concerning neurotrophins and their receptors, including our personal contribution which is essentially focused on the stress response.     

Neurotrophins and neurodegeneration

There is growing evidence that reduced neurotrophic support is a significant factor in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). In this review we discuss the structure and functions of neurotrophins such as nerve growth factor, and the role of these proteins and their tyrosine kinase (Trk) receptors in the aetiology and therapy of such diseases. Neurotrophins regulate development and the maintenance of the vertebrate nervous system. In the mature nervous system they affect neuronal survival and also influence synaptic function and plasticity. The neurotrophins are able to bind to two different receptors: all bind to a common receptor p75NTR, and each also binds to one of a family of Trk receptors. By dimerization of the Trk receptors, and subsequent transphosphorylation of the intracellular kinase domain, signalling pathways are activated. We discuss here the structure and function of the neurotrophins and how they have been, or may be, used therapeutically in AD, PD, Huntington's diseases, ALS and peripheral neuropathy. Neurotrophins are central to many aspects of nervous system function. However they have not truly fulfilled their therapeutic potential in clinical trials because of the difficulties of protein delivery and pharmacokinetics in the nervous system. With the recent elucidation of the structure of the neurotrophins bound to their receptors it will now be possible, using a combination of in silico technology and novel screening techniques, to develop small molecule mimetics with much improved pharmacotherapeutic profiles.     

Regulation of neurogenesis by neurotrophins in developing spinal sensory ganglia

Neurons and glia in spinal sensory ganglia derive from multipotent neural crest-derived stem cells. In contrast to neural progenitor cells in the central nervous system, neural crest progenitors coexist with differentiated sensory neurons all throughout the neurogenic period. Thus, developing sensory ganglia are advantageous for determining the possible influence of cell-cell interactions in the regulation of precursor proliferation and neurogenesis. Neurotrophins are important regulators of neuronal survival in the developing vertebrate nervous system and, in addition, they appear to influence precursor behavior in vitro. Studies in mice carrying mutations in neurotrophin genes provide a good system in which to analyze essential actions of these factors on the different developing neural populations.     

Ternary complex with Trk, p75, and an ankyrin-rich membrane spanning protein

Neurotrophins play many critical roles in regulating neuronal plasticity, survival, and differentiation in the nervous system. Neurotrophins recognize two different receptors, the Trk receptor tyrosine kinase and the p75 neurotrophin receptor, which are associated closely. Several adaptor proteins are associated with each receptor. An ankyrin-rich membrane spanning protein (ARMS), originally identified as a substrate for protein kinase D (Kidins220) and as a p75 interacting protein, serves as a novel downstream target of Trk receptor tyrosine kinases. Kidins220/ARMS is co-expressed frequently with Trk and p75 and represents the only membrane-associated protein known to interact with both receptors. We report here that a ternary complex can be formed between Trk, p75, and Kidins220/ARMS. The extracellular domains of the TrkA and the p75 receptors are necessary for their association, whereas the juxtamembrane region of p75 was responsible for the interaction with Kidins220/ARMS. Interestingly, increasing the level of Kidins220/ARMS expression resulted in a decreased association of TrkA with p75. These findings thus suggest that Kidins220/ARMS plays an important role in regulating interactions between Trk and p75 neurotrophin receptors.     

Neurotrophins: The therapeutic potential and concept of minipeptides

Neurotrophins belong to a family of polypeptides that exert control over many aspects of the survival, development, and functioning of structures within the central and peripheral nervous system. Neurotrophins, the nerve growth factor (NGF), the brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), as well as extracellular tyrosine kinase receptors (TrkA, TrkB, and TrkC) are specific targets for therapeutic intervention during different diseases. All these neurotrophins also bind to the p75 receptor, which has many functions depending on the type of cell where it is present. The diversity of neurotrophin effects is determined by ligand-receptor binding and the type of signaling responses that are specific for this interaction. NGF and other neurotrophins are involved in many pathological conditions. It has been shown that an insufficient level of neurotrophins in certain brain structures may be not only an initial cause of Alzheimer??s disease but also may be typical for cerebrovascular dysfunction, brain trauma, cognitive impairments, etc. The therapeutic potential of neurotrophins has been shown in many studies in the last decade but the effectiveness of neurotrophic therapy is limited by the poor diffusion of molecules across the blood-brain barrier and toxic adverse effects. The solution to this problem may be the creation of minipeptides and peptidomimetics that affect the activity of tyrosine-kinase receptors. Some of these structures are combinations of cyclic pentapeptides that facilitate interaction with Trk receptors and exert neuroprotective activity. In this review, we discuss the clinical and experimental data on the results of an alternative strategy that uses these peptidomimetics. These compounds comprise a new group of perspective agents in the therapy of neurodegenerative disorders.     

Trk B signalling controls LTP but not LTD expression in the developing rat visual cortex

Neurotrophins have been suggested to act as liaison molecules between activity-dependent synaptic plasticity and the establishment of patterns of synaptic connectivity during postnatal developmental in different brain areas, including the visual cortex. In particular, recent studies have shown that Trk B ligands are involved in the formation of the ocular dominance columns during postnatal development. Here, we examined the contribution of endogenous Trk B activation to the regulation of different forms of synaptic plasticity including long-term potentiation (LTP), long-term depression (LTD) and LTP after LTD in the developing visual cortex. Rat cortical slices were incubated with a soluble form of Trk B receptor (TrkB IgG) preventing Trk B activation by endogenous ligands. LTP expression was also studied at P23 (postnatal), when the expression of brain-derived neurotrophic factor (BDNF) reaches a peak and the LTP expression is normally downregulated. The present results demonstrate that Trk B activation is required for the long-term maintenance, > 30 min, of both LTP and LTP after LTD at P17. At P23, a higher concentration of TrkB IgG was necessary to impair LTP. In contrast, neither amplitude nor duration of LTD were affected by Trk B ligands blockade. Taken together, these results indicate that endogenous Trk B ligands are necessary for the expression of LTP but not LTD at a critical time during postnatal cortical development.     

Formation and evolution of the chordate neurotrophin and Trk receptor genes

Neurotrophins are structurally related neurotrophic polypeptide factors that regulate neuronal differentiation and are essential for neuronal survival, neurite growth and plasticity. It has until very recently been thought that the neurotrophin system appeared with the vertebrate species, but identification of a cephalochordate neurotrophin receptor (Trk), and more recently neurotrophin sequences in several genomes of deuterostome invertebrates, show that the system already existed at the stem of the deuterostome group. Comparative genomics supports the hypothesis that two whole genome duplications produced many of the vertebrate gene families, among those the neurotrophin and Trk families. It remains to be proven to what extent the whole genome duplications have driven macroevolutionary change, but it appears certain that the formation of the multi-gene copy neurotrophin and Trk receptor families at the stem of vertebrates has provided a foundation from which the various functions and pleiotropic effects produced by each of the four extant neurotrophins have evolved.