Neuron glia biology最新文献

The evolution of a character is better appreciated if examples of convergent emergence of the same character are available for comparison. Three instances are known among invertebrates of the evolution of axonal sheaths possessing the functional properties and many of the structural properties of vertebrate myelin. Comparison of these invertebrate myelins raises the question of what structural features must a sheath possess in order to produce the two principal functional characteristics of impulse speed enhancement and energy savings. This essay reviews the features recognized by early workers as pertaining to myelin in vertebrate and invertebrate alike: osmiophilia, negative birefringence and saltatory conduction. It then examines common features revealed by the advent of electron microscopy: multiplicity of lipid membranes, condensation of those membranes, specialized marginal seals, and nodes. Next it examines the robustness of these features as essential components of a speed-enhancing sheath. Features that are not entirely essential for speed enhancement include membrane compaction, spiral wrapping of layers, glial cell involvement, non-active axonal membrane, and even nodes and perinodal sealing. This permissiveness is discussed in relation to the possible evolutionary origin of myelin.

The protein composition of myelin in the central nervous system (CNS) has changed at the evolutionary transition from fish to tetrapods, when a lipid-associated transmembrane-tetraspan (proteolipid protein, PLP) replaced an adhesion protein of the immunoglobulin superfamily (P0) as the most abundant constituent. Here, we review major steps of proteolipid evolution. Three paralog proteolipids (PLP/DM20/DMalpha, M6B/DMgamma and the neuronal glycoprotein M6A/DMbeta) exist in vertebrates from cartilaginous fish to mammals, and one (M6/CG7540) can be traced in invertebrate bilaterians including the planktonic copepod Calanus finmarchicus that possess a functional myelin equivalent. In fish, DMalpha and DMgamma are coexpressed in oligodendrocytes but are not major myelin components. PLP emerged at the root of tetrapods by the acquisition of an enlarged cytoplasmic loop in the evolutionary older DMalpha/DM20. Transgenic experiments in mice suggest that this loop enhances the incorporation of PLP into myelin. The evolutionary recruitment of PLP as the major myelin protein provided oligodendrocytes with the competence to support long-term axonal integrity. We suggest that the molecular shift from P0 to PLP also correlates with the concentration of adhesive forces at the radial component, and that the new balance between membrane adhesion and dynamics was favorable for CNS myelination.

Nogo-A is possibly the best characterized myelin-derived inhibitor of nerve growth in the adult central nervous system (CNS). It is a member of the ancient reticulon family of mainly endoplasmic reticulum resident proteins with representatives found throughout the eukaryotic domain. Orthologs of the nogo gene were identified in tetrapods and teleost fish but none have been detected in invertebrates. Evolution of the nogo gene has been non-homogeneous. The exon-intron arrangement is conserved from amphibians (Xenopus) to mammals, but partly deviates from that found in several teleost fish species, indicating that the recruitment of nogo exons proceeded along at least two independent lines during early vertebrate evolution. This might have far-reaching consequences. Tetrapod nogo orthologs encode two neurite growth inhibitory domains whereas in fish nogo only one of the inhibitory domains is present. These distinct paths in nogo evolution have potentially contributed to the regeneration permissive CNS in fish as opposed to the non-regenerating CNS in higher vertebrates.

One of the special attributes of vertebrates is their myelinated nervous system. By increasing the conduction velocity of axons, myelin allows for increased body size, rapid movement and a large and complex brain. In the central nervous system (CNS), oligodendrocytes (OLs) are the myelin-forming cells. The transcription factors OLIG1 and OLIG2, master regulators of OL development, presumably also played a seminal role during the evolution of the genetic programme leading to myelination in the CNS. From the available ontogenetic and phylogenetic data we attempt to reconstruct the evolutionary events that led to the emergence of the Olig gene family and speculate about the links between Olig genes, their specific cis-regulatory elements and myelin evolution. In addition, we report a putative myelin basic protein (MBP) ancestor in the lancelet Branchiostoma floridae, which lacks compact myelin. The lancelet 'Mbp' gene lacks the OLIG1/2- and SOX10-binding sites that characterize vertebrate Mbp homologs, raising the possibility that insertion of cis-regulatory elements might have been involved in evolution of the myelinating programme.

Current concepts of invertebrate phylogeny are reviewed. Annelida and Arthropoda, previously regarded as closely related, are now placed in separate clades. Myelin, a sheath of multiple layers of membranes around nerve axons, is found in members of the Annelida, Arthropoda and Chordata. The structure, composition and function of the sheaths in Annelida and Arthropoda are examined and evidence for the separate evolutionary origins of myelin in the three clades is presented. That myelin has arisen independently at least three times, namely in Annelids, Arthropodas and Chordates, provides a remarkable example of convergent evolution.

To analyze myelin structure and the composition of myelinated tissue in the African lungfish (Protopterus dolloi), we used a combination of ultrastructural and biochemical techniques. Electron microscopy showed typical multilamellar myelin: CNS sheaths abutted one another, and PNS sheaths were separated by endoneurial collagen. The radial component, prominent in CNS myelin of higher vertebrates, was suggested by the pattern of staining but was poorly organized. The lipid and myelin protein compositions of lungfish tissues more closely resembled those of teleost than those of higher vertebrates (frog, mouse). Of particular note, for example, lungfish glycolipids lacked hydroxy fatty acids. Native myelin periodicities from unfixed nerves were in the range of those for higher vertebrates rather than for teleost fish. Lungfish PNS myelin had wider inter-membrane spaces compared with other vertebrates, and lungfish CNS myelin had spaces that were closer in value to those in mammalian than to amphibian or teleost myelins. The membrane lipid bilayer was narrower in lungfish PNS myelin compared to other vertebrates, whereas in the CNS myelin the bilayer was in the typical range. Lungfish PNS myelin showed typical compaction and swelling responses to incubation in acidic or alkaline hypotonic saline. The CNS myelin, by contrast, did not compact in acidic saline but did swell in the alkaline solution. This lability was more similar to that for the higher vertebrates than for teleost.

Astrocytes were classically considered as simple supportive cells for neurons without a significant role in information processing by the nervous system. However, considerable amounts of evidence obtained by several groups during the past years demonstrated the existence of a bidirectional communication between astrocytes and neurons, which prompted a re-examination of the role of astrocytes in the physiology of the nervous system. While neurons base their excitability on electrical signals generated across the membrane, astrocytes base their cellular excitability on variations of the Ca2+ concentration in the cytosol. This article discusses our current knowledge of the properties of the synaptically evoked astrocyte Ca2+ signal, which reveals that astrocytes display integrative properties for synaptic information processing. Astrocytes respond selectively to different axon pathways, discriminate between the activity of different synapses and their Ca2+ signal is non-linearly modulated by the simultaneous activity of different synaptic inputs. Furthermore, this Ca2+ signal modulation depends on astrocyte cellular intrinsic properties and is bidirectionally regulated by the level of synaptic activity. Finally, astrocyte Ca2+ elevations can trigger the release of gliotransmitters, which modulate neuronal activity as well as synaptic transmission and plasticity, hence granting the bidirectional communication with neurons. Consequently, astrocytes can be considered as cellular elements involved in information processing by the nervous system.

Activity-dependent signaling between neurons and astrocytes contributes to experience-dependent plasticity and development of the nervous system. However, mechanisms responsible for neuron-glial interactions and the releasable factors that underlie these processes are not well understood. The pro-inflammatory cytokine, leukemia-inhibitory factor (LIF), is transiently expressed postnatally by glial cells in the hippocampus and rapidly up-regulated by enhanced neural activity following seizures. To test the hypothesis that spontaneous neural activity regulates glial development in hippocampus via LIF signaling, we blocked spontaneous activity with the sodium channel blocker tetrodotoxin (TTX) in mixed hippocampal cell cultures in combination with blockers of LIF and purinergic signaling. TTX decreased the number of GFAP-expressing astrocytes in hippocampal cell culture. Furthermore, blocking purinergic signaling by P2Y receptors contributed to reduced numbers of astrocytes. Blocking activity or purinergic signaling in the presence of function-blocking antibodies to LIF did not further decrease the number of astrocytes. Moreover, hippocampal cell cultures prepared from LIF -/- mice had reduced numbers of astrocytes and activity-dependent neuron-glial signaling promoting differentiation of astrocytes was absent. The results show that endogenous LIF is required for normal development of hippocampal astrocytes, and this process is regulated by spontaneous neural impulse activity through the release of ATP.

NG2 cells represent a unique glial cell population that is distributed widely throughout the developing and adult CNS and is distinct from astrocytes, mature oligodendrocytes and microglia. The ability of NG2 cells to differentiate into myelinating oligodendrocytes has been documented in vivo and in vitro. We reported recently that NG2 cells in the forebrain differentiate into myelinating oligodendrocytes but into a subpopulation of protoplasmic astrocytes (Zhu et al., 2008). However, the in vivo fate of NG2 cells in the spinal cord and cerebellum has remained unknown. To investigate the fate of NG2 cells in caudal central nervous system (CNS) regions in vivo, we examined the phenotype of cells that express EGFP in mice that are double transgenic for NG2CreBAC and the Cre reporter Z/EG. The fate of NG2 cells can be studied in these mice by permanent expression of EGFP in cells that have undergone Cre-mediated recombination in NG2 cells. We find that NG2 cells give rise to oligodendrocytes in both gray and white matter of the spinal cord and cerebellum, and to protoplasmic astrocytes in the gray matter of the spinal cord. However, NG2 cells do not give rise to astrocytes in the white matter of the spinal cord and cerebellum. These observations indicate that NG2 cells serve as precursor cells for oligodendrocytes and a subpopulation of protoplasmic astrocytes throughout the rostrocaudal axis of the CNS.

Mounting evidence demonstrates that glial cells might have important roles in regulating the physiology and behavior of adult animals. We summarize some of this evidence here, with an emphasis on the roles of glia of the differentiated nervous system in controlling neuronal excitability, behavior and plasticity. In the review we highlight studies in Drosophila and discuss results from the analysis of mammalian astrocytes that demonstrate roles for glia in the adult nervous system.