scholarly journals Synapse formation in the adult brain after lesions and after transplantation of embryonic tissue

1990 ◽  
Vol 153 (1) ◽  
pp. 277-287
Author(s):  
G. Raisman ◽  
P. M. Field

Some years ago it was demonstrated that when the adult rat septal nuclei are partially deafferented the remaining afferent fibres form new connections. The conclusion that new synaptic connections form in the adult central nervous system (CNS) was greeted initially with much scepticism, later with over-enthusiasm and unwarranted generalisation to all lesion situations, together with even less warranted attribution of various beneficial functional properties. Today, as the pendulum swings into a more reasonable position, some of the original observations, which at the time attracted little attention, have become more interesting. (1) The observation that in the normal septal nuclei the ratio of spine to shaft synapses is extraordinarily constant (to an accuracy better than 1%) from one animal to another. How could such almost crystalline rigidity of structure be produced in normal development and maintained in the face of major lesion-induced changes in connectivity? (2) The observation that synaptic re-occupation by sprouting axons restores exactly the normal number of synapses, presumably indicating that the neurones have a fixed number (as well as spine/shaft distribution) of postsynaptic sites. Thus, the septal lesion paradigm is as strong a method for investigating synaptic rigidity as for investigating plasticity. In the intervening years, the use of embryo to adult transplantation has made it obvious that considerable reconstruction of adult brain synaptology is possible, and that many of the normal rules of connectivity are maintained (most prominently for the ‘point-to-point’ axonal systems). What could lead to further fruitful investigation is the extent to which the observations (e.g. relating to hierarchies of axonal preference, the need for denervation, and the involvement of glial cells) in partially deafferented adult systems, such as the septal nuclei, are retained, or modified, in face of the ingrowing fibres from embryonic transplants.

2008 ◽  
Vol 60 (4) ◽  
pp. 581-591
Author(s):  
Sanja Dacic ◽  
Sanja Pekovic ◽  
Maja Stojiljkovic ◽  
Irena Lavrnja ◽  
Danijela Stojkov ◽  
...  

The central nervous system has a limited capacity for self-repair after damage. However, the neonatal brain has agreater capacity for recovery than the adult brain. These differences in the regenerative capability depend on local environmental factors and the maturational stage of growing axons. Among molecules which have both growth-promoting and growth-inhibiting activities is the heterogeneous class of chondroitin sulfate proteoglycans (CSPGs). In this paper, we investigated the chondroitin-4 and chondroitin-6 sulfate proteoglycan expression profile after left sensorimotor cortex ablation of the neonatal and adult rat brain. Immunohistochemical analysis revealed that compared to the normal uninjured cortex, lesion provoked up regulation of CSPGs showing a different pattern of expression in the neonatal vs. the adult brain. Punctuate and membrane-bound labeling was predominate after neonatal lesion, where as heavy deposition of staining in the extracellular matrix was observed after adult lesion. Heavy deposition of CSPG immunoreactivity around the lesionsite in adult rats, in contrast to a less CSPG-rich environment in neonatal rats, indicated that enhancement of the recovery process after neonatal injury is due to amore permissive environment.


1992 ◽  
Vol 118 (4) ◽  
pp. 889-900 ◽  
Author(s):  
G Wolswijk ◽  
M Noble

We have shown previously that oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells isolated from adult rat optic nerves can be distinguished in vitro from their perinatal counterparts on the basis of their much slower rates of division, differentiation, and migration when grown in the presence of cortical astrocytes or PDGF. This behavior is consistent with in vivo observations that there is only a modest production of oligodendrocytes in the adult CNS. As such a behavior is inconsistent with the likely need for a rapid generation of oligodendrocytes following demyelinating damage to the mature CNS, we have been concerned with identifying in vitro conditions that allow O-2Aadult progenitor cells to generate rapidly large numbers of progeny cells. We now provide evidence that many slowly dividing O-2Aadult progenitor cells can be converted to rapidly dividing cells by exposing adult optic nerve cultures to both PDGF and bFGF. In addition, these O-2Aadult progenitor cells appear to acquire other properties of O-2Aperinatal progenitor cells, such as bipolar morphology and high rate of migration. Although many O-2Aadult progenitor cells in cultures exposed to bFGF alone also divide rapidly, these cells are multipolar and migrate little in vitro. Oligodendrocytic differentiation of O-2Aadult progenitor cells, which express receptors for bFGF in vitro, is almost completely inhibited in cultures exposed to bFGF or bFGF plus PDGF. As bFGF and PDGF appear to be upregulated and/or released after injury to the adult brain, this particular in vitro response of O-2Aadult progenitor cells to PDGF and bFGF may be of importance in the generation of large numbers of new oligodendrocytes in vivo following demyelination.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Hannah N. Robeson ◽  
Hayley R. Lau ◽  
Laura A. New ◽  
Jasmin Lalonde ◽  
John N. Armstrong ◽  
...  

Abstract Background Mammalian Shc (Src homology and collagen) proteins comprise a family of four phosphotyrosine adaptor molecules which exhibit varied spatiotemporal expression and signaling functions. ShcD is the most recently discovered homologue and it is highly expressed in the developing central nervous system (CNS) and adult brain. Presently however, its localization within specific cell types of mature neural structures has yet to be characterized. Results In the current study, we examine the expression profile of ShcD in the adult rat CNS using immunohistochemistry, and compare with those of the neuronally enriched ShcB and ShcC proteins. ShcD shows relatively widespread distribution in the adult brain and spinal cord, with prominent levels of staining throughout the olfactory bulb, as well as in sub-structures of the cerebellum and hippocampus, including the subgranular zone. Co-localization studies confirm the expression of ShcD in mature neurons and progenitor cells. ShcD immunoreactivity is primarily localized to axons and somata, consistent with the function of ShcD as a cytoplasmic adaptor. Regional differences in expression are observed among neural Shc proteins, with ShcC predominating in the hippocampus, cerebellum, and some fiber tracts. Interestingly, ShcD is uniquely expressed in the olfactory nerve layer and in glomeruli of the main olfactory bulb. Conclusions Together our findings suggest that ShcD may provide a distinct signaling contribution within the olfactory system, and that overlapping expression of ShcD with other Shc proteins may allow compensatory functions in the brain.


2020 ◽  
Vol 21 (4) ◽  
pp. 1539 ◽  
Author(s):  
Ciro De Luca ◽  
Anna Maria Colangelo ◽  
Assunta Virtuoso ◽  
Lilia Alberghina ◽  
Michele Papa

The synaptic cleft has been vastly investigated in the last decades, leading to a novel and fascinating model of the functional and structural modifications linked to synaptic transmission and brain processing. The classic neurocentric model encompassing the neuronal pre- and post-synaptic terminals partly explains the fine-tuned plastic modifications under both pathological and physiological circumstances. Recent experimental evidence has incontrovertibly added oligodendrocytes, astrocytes, and microglia as pivotal elements for synapse formation and remodeling (tripartite synapse) in both the developing and adult brain. Moreover, synaptic plasticity and its pathological counterpart (maladaptive plasticity) have shown a deep connection with other molecular elements of the extracellular matrix (ECM), once considered as a mere extracellular structural scaffold altogether with the cellular glue (i.e., glia). The ECM adds another level of complexity to the modern model of the synapse, particularly, for the long-term plasticity and circuit maintenance. This model, called tetrapartite synapse, can be further implemented by including the neurovascular unit (NVU) and the immune system. Although they were considered so far as tightly separated from the central nervous system (CNS) plasticity, at least in physiological conditions, recent evidence endorsed these elements as structural and paramount actors in synaptic plasticity. This scenario is, as far as speculations and evidence have shown, a consistent model for both adaptive and maladaptive plasticity. However, a comprehensive understanding of brain processes and circuitry complexity is still lacking. Here we propose that a better interpretation of the CNS complexity can be granted by a systems biology approach through the construction of predictive molecular models that enable to enlighten the regulatory logic of the complex molecular networks underlying brain function in health and disease, thus opening the way to more effective treatments.


2020 ◽  

Media environments and public communication are becoming increasingly digital, and the coronavirus crisis has accelerated this development. The changes connected to this relate to key ethical values and norms, such as informational autonomy, privacy and transparency. This not only demands an empirically based discourse underpinned by theory, but also consideration of what courses of action may result from this and, from a normative perspective, what recommendations for action can be formulated. Media and communication ethics is thus confronted with some fundamental questions: Are its existing concepts and models still viable in the face of these digitally induced changes? Should they be altered or expanded? Where should this ‘reloading’ start? The contributions in this book develop important guidelines in this respect, for example on ethical demands on innovations and on truth and our world view in this post-factual society. With contributions by Klaus-Dieter Altmeppen, Christian Augustin Christoph Bieber, Roger Blum, Ekkehard Brüggemann Bernhard Debatin, Tobias Eberwein, Rainer Erlinger, Daniel Fiene, Alexander Filipović, Andrea Günter, Matthias Karmasin, Nina Köberer, Larissa Krainer, Geert Lovink, Colin Porlezza, Marlis Prinzing, Matthias Rath, Pierre Rieder, Christian Schicha, Josephine B. Schmitt, Sonja Schwetje, Saskia Sell, Ingrid Stapf, Hansi Voigt, Thomas Zeilinger and Marc Ziegele.


1999 ◽  
Vol 23 (3) ◽  
pp. 299-306 ◽  
Author(s):  
S Valenti ◽  
S Thellung ◽  
T Florio ◽  
M Giusti ◽  
G Schettini ◽  
...  

The site of inhibition, by melatonin, of GnRH-dependent testosterone secretion was investigated in adult rat Leydig cells cultured in vitro. The various effects downstream of the binding of GnRH to its own receptor were isolated and mimicked by specific drugs. Testosterone secretion was then evaluated after 3 h stimulation with GnRH, thapsigargin (1 microM), phorbol-12-myristate-13-acetate (100 nM), arachidonic acid (20 microM), and ionomycin (1 microM) in the presence or absence of melatonin (215 nM). The effect of melatonin on the GnRH-induced changes in cytoplasmic calcium concentration ([Ca(2+)](i)) was also studied, using Fura-2 as fluorescent Ca(2+) indicator. Melatonin attenuated the increase in [Ca(2+)](i) and inhibited the testosterone secretion induced by GnRH, but not that induced by ionomycin. Both ionomycin and thapsigargin potentiated GnRH-induced testosterone secretion; however, ionomycin, but not thapsigargin, partially prevented the inhibitory effect of melatonin on cells stimulated with GnRH. The effect of melatonin was probably dependent on the binding of melatonin to its Gi-protein-coupled receptor, as the inhibitory effect on GnRH-induced secretion was supressed in cells pretreated with pertussis toxin in a concentration of 180 ng/ml for 20 h. Assay of 17-hydroxy-progesterone showed that, irrespective of the treatment, cells cultured with melatonin secreted greater amounts than controls. We conclude that melatonin reduces GnRH-induced testosterone secretion by 1) decreasing [Ca(2+)](i), through impairment of the GnRH-dependent release of Ca(2+) from intracellular stores and 2) blocking 17-20 desmolase enzymatic activity, an effect that occurs irrespective of changes in [Ca(2+)](i).


2011 ◽  
Vol 286 (27) ◽  
pp. 24385-24393 ◽  
Author(s):  
Martin Kriebel ◽  
Jennifer Metzger ◽  
Sabine Trinks ◽  
Deepti Chugh ◽  
Robert J. Harvey ◽  
...  

Cell adhesion molecules regulate synapse formation and maintenance via transsynaptic contact stabilization involving both extracellular interactions and intracellular postsynaptic scaffold assembly. The cell adhesion molecule neurofascin is localized at the axon initial segment of granular cells in rat dentate gyrus, which is mainly targeted by chandelier cells. Lentiviral shRNA-mediated knockdown of neurofascin in adult rat brain indicates that neurofascin regulates the number and size of postsynaptic gephyrin scaffolds, the number of GABAA receptor clusters as well as presynaptic glutamate decarboxylase-positive terminals at the axon initial segment. By contrast, overexpression of neurofascin in hippocampal neurons increases gephyrin cluster size presumably via stimulation of fibroblast growth factor receptor 1 signaling pathways.


Neuroscience ◽  
1988 ◽  
Vol 24 (2) ◽  
pp. 673-686 ◽  
Author(s):  
T. Lømo ◽  
S. Pockett ◽  
H. Sommerschild
Keyword(s):  

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