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神经科学

位置: 首页 > 研究领域 > 神经科学
  • 突触与突触蛋白

    In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another cell (neural or otherwise). Synapses are essential to neuronal function, The key to neural function is the synaptic signaling process. Synaptic signals to other neurons are transmitted by the axon; signals from other neurons are received by the soma and dendrites. Synapses can be excitatory or inhibitory and will either increase or decrease activity in the target neuron. The human brain contains about 100 billion neurons and 100-500 trillion synapses; each neuron may have thousands of input synaptic connections. It is the complex integration of these synaptic signals that controls all of the body functions including learning, memory, sensory integration, motor coordination, and emotional responses.

    In an electrical synapse, the presynaptic and postsynaptic cell membranes are connected by special channels called gap junctions that are capable of passing electric current, causing voltage changes in the presynaptic cell to induce voltage changes in the postsynaptic cell. The main advantage of an electrical synapse is the rapid transfer of signals from one cell to the next. In a chemical synapse, the presynaptic neuron releases a chemical called a neurotransmitter that binds to receptors located in the postsynaptic cell, usually embedded in the plasma membrane. The neurotransmitter may initiate an electrical response or a secondary messenger pathway that may either excite or inhibit the postsynaptic neuron. Because of the complexity of receptor signal transduction, chemical synapses can have complex effects on the postsynaptic cell.

     

  • 神经营养因子与受体

    Neurotrophic factors are a family of proteins that are responsible for the growth and survival of developing neurons and the maintenance of mature neurons. Recent research has shown that neurotrophic factors promote the initial growth and development of neurons in the central nervous system and peripheral nervous system and that they are capable of regrowing damaged neurons in test tubes and animal models. Neurotrophic factors comprise a broad family, each family has its own distinct signaling family though the cellular responses elicited often do overlap. Neurotrophic factors are essential for keeping neurons alive and properly connected. During development, these factors play a critical role in nourishing the neurons in the spinal cord that connect to the muscle cells to prevent the death of the nerve cell. In addition, neurotrophic factors regulate growth of neurons, associated metabolic functions such as protein synthesis, and the ability of the neuron to make the neurotransmitters that carry chemical signals which allow the neuron to communicate with other neurons or with other targets.

    The first neurotrophic factor family discovered was the neurotrophins which consist of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). Each of the four mammalian neurotrophins has been shown to activate one or more of the three members of the tropomyosin-related kinase (Trk) family of receptor tyrosine kinases (TrkA, TrkB and TrkC). In addition, each neurotrophin activates p75 neurotrophin receptor (p75NTR), a member of the tumour necrosis factor receptor superfamily. Members of numerous other proteins also regulate neural survival, development and function through activation of receptor tyrosine kinases, most notably the glial cell-derived neurotrophic factor (GDNF) family. There are at least four members of this family including GDNF, neurturin, artemin, and persephin.

    Neurotrophic factors control the survival and development of neurons. Currently, neurotrophic factors are being intensely studied for use in bioartificial nerve conduits because they also play important roles in regulating axon growth, dendrite cell growth and pruning and the expression of proteins, such as ion channels, transmitter biosynthetic enzymes and neuropeptide transmitters that are essential for normal neuronal function. The neurotrophic factors may or may not be immobilized to the scaffold structure, though immobilization is preferred because it allows for the creation of permanent, controllable gradients. In some cases, such as neural drug delivery systems, they are loosely immobilized such that they can be selectively released at specified times and in specified amounts.

     

     

  • 神经细胞标志物

    Neuron also known as a neurone or nerve cell is an electrically excitable cell that processes and transmits information through electrical and chemical signals. A chemical signal occurs via a synapse, a specialized connection with other cells. Neurons connect to each other to form neural networks. Neurons are the core components of the nervous system, which includes the brain, spinal cord, and peripheralganglia. A number of specialized types of neurons exist: sensory neurons respond to touch, sound, light and numerous other stimuli affecting cells of the sensory organs that then send signals to the spinal cord and brain. Motor neuronsreceive signals from the brain and spinal cord, cause muscle contractions, and affect glands. Interneurons connect neurons to other neurons within the same region of the brain or spinal cord.

    All neurons are electrically excitable, maintaining  voltage gradients across their membranes by means of metabolically driven ion pumps, which combine with ion channels embedded in the membrane to generate  intracellular-versus-extracellular concentration differences of ions such as sodium, potassium, chloride, and calcium. Changes in the cross-membrane voltage can alter the function of voltage-dependent ion channels. If the voltage changes by a large enough amount, an all-or-none electrochemical pulse called an action potential is generated, which travels rapidly along the cell's axon, and activates synaptic connections with other cells when it arrives.

    Neurons do not undergo cell division. In most cases, neurons are generated by special types of stem cells. Astrocytes, a type of glial cell, have also been observed to turn into neurons by virtue of the stem cell characteristic pluripotency. In humans, neurogenesis largely ceases during adulthood—but in two brain areas, the hippocampus and olfactory bulb, there is strong evidence for generation of substantial numbers of new neurons.

  • 神经退行与神经退行性疾病

    Neurodegeneration is the umbrella term for the progressive loss of structure or function of neurons, including death of neurons. Neurodegenerative diseases constitute one of the major challenges of modern medicine, including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Lyme disease, Parkinson's disease, and so on. These diseases are relatively common and often highly debilitating. However, the mechanisms responsible for their pathologies are poorly understood, and there are currently no effective preventative therapies. As research progresses, many similarities appear which relate these diseases to one another on a sub-cellular level. Discovering these similarities offers hope for therapeutic advances that could ameliorate many diseases simultaneously.  Recent research on the genetic pathways leading to pathology with animal models (mice and Drosophila) begun to identify molecular mechanisms underlying neurodegenerative disorders.

    Many neurodegenerative diseases are caused by genetic mutations, most of which are located in completely unrelated genes. In many of the different diseases, the mutated gene has a common feature: a repeat of the CAG nucleotide triplet. CAG encodes for the amino acid glutamine. A repeat of CAG results in a polyglutamine (polyQ) tract. Research on the neurodegenerative disease, spinocerebellar ataxia type 1 (SCA1), found out that polyglutamine expansion contributes to disease by both a gain-of-function mechanism and partial loss of function of the SCA1 encoded protein ATXN1. Another important pathological mechanism is alpha-synuclein aggregation. Alpha-synuclein is the primary structural component of Lewy body fibrils. Normally an unstructured soluble protein, alpha-synuclein can aggregate to form insoluble fibrils in pathological conditions characterized by Lewy bodies, such as Parkinson's disease, dementia with Lewy bodiesand multiple system atrophy. Alpha-synuclein pathology is also found in both sporadic and familial cases with Alzheimer's disease.

    Strong evidence underscores the tight link between oxidative stress and neurodegenerative disease pathogenesis, including in four of the well known diseases Alzheimer's, Parkinson's, Amyotrophic lateral sclerosis, and Huntington's. Studies suggest that oxidative modification of K+ channels might be a general principle underlying aging and neurodegeneration. The formation of intracellular aggregates by toxic proteins is also a cause of many late-onset neurodegenerative diseases, including Parkinson's disease and Huntington's disease. The degradation pathways acting on such aggregate-prone cytosolic proteins include the ubiquitin-proteasome system and macroautophagy. Dysfunction of the ubiquitin-proteasome or macroautophagy pathways might contribute to the pathology of various neurodegenerative conditions. In addition, current research indicates that cell death in neurodegeneration is generally due to apoptosis and most commonly through the intrinsic mitochondrial pathway.

     

     

  • 神经干细胞标志物

    Stem cells are characterized by their capability to differentiate into multiple cell types via exogenous stimuli from their environment. Neural stem cells (NSCs) are multipotent stem cells that are capable of self-renewing and differentiating into the three main central nervous system (CNS) lineages: neurons, astrocytes, and oligodendrocytes. Neural stem cells undergo proliferative symmetric and asymmetric divisions to replenish themselves and to produce intermediate neural progenitors (INPs), NSCs are stimulated to begin differentiation via exogenous cues from the microenvironment, or stem cell niche. This capability of the NSCs to replace lost or damaged neural cells is called neurogenesis. Some neural cells are migrated from the SVZ along the rostral migratory stream which contains a marrow-like structure with ependymal cells and astrocytes when stimulated. Thus, a balance of symmetric and asymmetric neural stem cell divisions regulates the number of neural stem cells, intermediate neural progenitors and produced neurons, and is critical for defining the adult brain.

  • 神经元细胞标志物

    The asymmetric mitosis neural stem cells (NSCs) produces one NSC and one neural progenitor cell (NPC), neural progenitor cell is a biological cell that, like a neural stem cell, has a tendency to differentiate into a specific type of cell, but is already more specific than a stem cell and is pushed to differentiate into its "target" cell. The most important difference between neural stem cells and neural progenitor cells is that neural stem cells can replicate indefinitely, whereas neural progenitor cells can divide only a limited number of times. However, the Controversy about the exact definition remains and the concept is still evolving.
    There are four types of neural progenitor cell. Neurogenesis in mammals commences with the induction of the neuroectoderm, which is followed by the formation of the neural plate, which folds to form the neural tube. These structures are composed of neuroepithelial progenitors (NEP) that are responsible for neurogenesis in the neural tube. NEPs also give rise to two other types of neural progenitor cell, radial glia and basal progenitors. Radial glia are the dominant progenitor cell type in the developing brain whereas basal progenitors are specifically located at the subventricular zone (SVZ) in the developing telencephalon. In the adult brain, adult progenitors in the subgranular zone (SGZ) of the dentate gyrus in the hippocampus and the SVZ of the lateral ventricles, are thought to functionally contribute to brain plasticity and repair.

  • 神经鞘细胞标志物

    Neural crest stem cells which are derived from ectoderm are transient, multipotent cells. Neural crest stem cells migrate from the roof plate of the neural tube where they originate, to generate a prodigious number of differentiated cell types including melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral and enteric neurons and glia.. After gastrulation, neural crest cells are specified at the border of the neural plate and the non-neural ectoderm. During neurulation, the borders of the neural plate, also known as the neural folds, converge at the dorsal midline to form the neural tube. Subsequently, neural crest cells from the roof plate of the neural tube undergo an epithelial to mesenchymal transition, delaminating from the neuroepithelium and migrating through the periphery where they differentiate into varied cell types.The emergence of neural crest was important in vertebrate evolution because many of its structural derivatives are defining features of the vertebrate clade. Neural crest cells break away from the neural plate or neural tube by changing their shape and properties from those of typical neuroepithelial cells to those of mesenchymal cells. The fate of the neural crest cells depends, to a large degree, on where they migrate to and settle. Understanding the molecular mechanisms of neural crest formation is important for our knowledge of human disease because of its contributions to multiple cell lineages. 

  • 轴突导向

    Axon guidance (also called axon pathfinding) is a subfield of neural development concerning the process by which axons extend to reach their correct targets. Axons often follow very precise paths in the nervous system, it is important in neural development, and how they manage to find their way so accurately is being researched. Axons are guided along specific pathways by attractive and repulsive cues in the extracellular environment. At the growing tip of axons, a highly motile structure, called growth cone, it "sniffs out" the extracellular environment for signals that instruct the axon which direction to grow. These signals, called guidance cues, can be fixed in place or diffusible; they can attract or repel axons. Growth cones contain receptors that recognize these guidance cues and interpret the signal into a chemotropic response. A combination of genetic and biochemical methods has led to the discovery of several important classes of axon guidance molecules and their receptors,including Ephrins, Netrins, Semaphorins and Slits. Netrins: Netrins are secreted molecules that can act to attract or repel axons by binding to their receptors, DCC and UNC5; Slits, semaphorins, and ephrins act primarily as repellents but can be attractive or adhesive in some contexts. In addition, many other guidance factors have been identified: neurotrophins, TGF-beta family members, BMPs, hepatocyte growth factor (HGF) factor, and additional candidate receptors include the protocadherin family, immunoglobulin family cell adhesion molecules (Ig-CAMs), neurexins, and odorant receptors. Guidance cues steer axons by regulating cytoskeletal dynamics in the growth cone through signaling pathways that are still not well understood. The general theoretical framework is that when a growth cone "senses" a guidance cue, the receptors activate various signaling molecules in the growth cone that eventually affect the cytoskeleton. If the growth cone senses a gradient of guidance cue, the intracellular signaling in the growth cone happens asymmetrically, so that cytoskeletal changes happen asymmetrically and the growth cone turns toward or away from the guidance cue.

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