subject:(Neurofascin)

1. Roche, Sarah Louise. Importance of axon-glial interactions for the normal postnatal development of the mouse peripheral nervous system.

Degree: PhD, 2015, University of Edinburgh

URL: http://hdl.handle.net/1842/15888

► The mouse nervous system undergoes a vast remodelling of synaptic connections postnatally, resulting in a reduced number of innervating axons to target cells within the… (more)

▼ The mouse nervous system undergoes a vast remodelling of synaptic connections postnatally, resulting in a reduced number of innervating axons to target cells within the first few weeks of life. This extensive loss of connections is known as synapse elimination and it plays a critical role in sculpting and refining neural connectivity throughout the nervous system, resulting in a finely tuned and well-synchronised network of innervation. This process has been well characterised at the mouse neuromuscular junction (NMJ), where synapse elimination takes place postnatally in all skeletal muscles. It has been well studied for the reasons that it is easily accessible for live imaging and post-mortem experimental analysis. Studies utilising this synapse to uncover regulators of synapse elimination have mainly focused on the importance of glial cell lysosomal activity, nerve conduction and target-derived growth factor supply. It is clear that non-axonal cell types play key roles in the success of developmental axon retraction at the NMJ, however the role of glial cells in the regulation of this process has not been fully explored, as lysosomal activity is thought of as a consequence of axon pruning rather than a molecular driver. Previous studies have shown that signals emanating from myelinating glial cells can modulate neurofilament composition and transport within the underlying axons. We know that these changes in neurofilament composition and transport are underway during developmental synapse elimination at the NMJ, so it seems logical to predict that myelinating glial cells may play a role in the regulation of axonal pruning. Myelinating glial cells are found along the entire length of lower motor neurons and form physical interactions with the underlying axons at regions known as paranodes. At the paranode, Neurofascin155 (Nfasc155: expressed by the myelinating glial cell) interacts with a Caspr/contactin complex (expressed by the axon). This site has been proposed as a likely site for axon-glial signalling due to the close apposition of the cell membranes. The main focus of this PhD project was to study the potential role of myelinating glial cells in the success of synapse elimination at the NMJ, using a mouse model of paranodal disruption (Nfasc155-/-). Chapters 3 and 4 show the results of this work. This work has revealed a novel role for glia in the modulation of synapse elimination at the mouse neuromuscular junction, mediated by Nfasc155 in the myelinating Schwann cell. Synapse elimination was profoundly delayed in Nfasc155-/- mice and was found to be associated with a non-canonical role for Nfasc155, as synapse elimination occurred normally in mice lacking the axonal paranodal protein Caspr. Loss of Nfasc155 was sufficient to disrupt axonal proteins contributing to cytoskeletal organisation and trafficking pathways in peripheral nerve of Nfasc155-/- mice and lower levels of neurofilament light (NF-L) protein in maturing motor axon terminals. Synapse elimination was delayed in mice lacking NF-L, suggesting…

Subjects/Keywords: 612.8; glial cells; neuromuscular junction; mouse peripheral nervous system; neurofascin

11 more images…

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Roche, S. L. (2015). Importance of axon-glial interactions for the normal postnatal development of the mouse peripheral nervous system. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/15888

Chicago Manual of Style (16^th Edition):

Roche, Sarah Louise. “Importance of axon-glial interactions for the normal postnatal development of the mouse peripheral nervous system.” 2015. Doctoral Dissertation, University of Edinburgh. Accessed January 16, 2021. http://hdl.handle.net/1842/15888.

MLA Handbook (7^th Edition):

Roche, Sarah Louise. “Importance of axon-glial interactions for the normal postnatal development of the mouse peripheral nervous system.” 2015. Web. 16 Jan 2021.

Vancouver:

Roche SL. Importance of axon-glial interactions for the normal postnatal development of the mouse peripheral nervous system. [Internet] [Doctoral dissertation]. University of Edinburgh; 2015. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/1842/15888.

Council of Science Editors:

Roche SL. Importance of axon-glial interactions for the normal postnatal development of the mouse peripheral nervous system. [Doctoral Dissertation]. University of Edinburgh; 2015. Available from: http://hdl.handle.net/1842/15888

2. Black, Jennifer. Discerning the Mechanism of Gamma Delta T Cell-Mediated Damage in Multiple Sclerosis: the Potential Role of Antibodies in Disease Pathogenesis .

Degree: 2015, University of Ottawa

URL: http://hdl.handle.net/10393/31925

► Background: Both the innate and adaptive immune systems contribute to autoimmune injury in multiple sclerosis (MS). We have been particularly interested in elucidating the role… (more)

▼ Background: Both the innate and adaptive immune systems contribute to autoimmune injury in multiple sclerosis (MS). We have been particularly interested in elucidating the role of the innate γδ T-cell population in MS pathogenesis. In particular, some γδ T-cells that express Fc receptors (FcR), such as CD16, that bind antibody are more prominent with MS disease progression and have been shown to exert cytolysis via antibody-dependent cellular cytotoxicity (ADCC). We postulated that if there were also relevant and detectable antibodies in MS patients that might engage these FcR-bearing γδ T-cells then this might be a purported mechanism of neuro-axonal injury. A search for antibodies specific to axonal elements in MS revealed the presence of antibodies to neurofascin (Nfasc). Methods: Anti-Nfasc antibody titres, and concentrations of the light and heavy chains of neurofilament (NfL and NfH, respectively), markers of neuro-axonal injury, were measured in the sera and cerebrospinal fluid (CSF) of MS patients using enzyme-linked immunosorbent assays (ELISA), including those that underwent autologous hematopoietic stem cell transplantation (aHSCT), both prior to and yearly for 3 years thereafter. HeLa cells were transfected with the axonal variant of Nfasc, Nfasc-186, and were utilized as targets in ADCC assays involving γδ T-cells as the effectors, and anti-Nfasc antibodies that were enriched from MS patient sera. Results: Positive anti-Nfasc antibody titres were detected in of 22% and 25% of MS patient sera and CSF, respectively. The most elevated serum titres were in secondary progressive MS (SPMS), and highest CSF titres in relapsing-remitting MS (RRMS) (p<0.05 and p<0.0001, respectively, vs. other neurological disease [OND] controls). Patient serum and CSF antibody titres correlated and, in the CSF, the titres correlated positively with the concentration of NfL. Though NfL and NfH concentrations declined markedly following aHSCT in the CSF, anti-Nfasc antibody titres failed to decline. When co-cultured with CD16+ γδ T-cells in the presence of MS patient-derived anti-Nfasc antibodies, the percent specific cytolysis of the Nfasc-transfected HeLa cells was significantly greater than that of the non-transfected control HeLa cells, at 18% and 1%, respectively, indicating cytolytic kill via ADCC. Summary: Anti-Nfasc antibodies were detectable in the sera and CSF of MS patients, and rarely in OND controls, suggesting they are relevant to MS. Higher titres in the serum support peripheral synthesis, while higher CSF titres in the relapsing phase, that correlate with serum titres, imply that antibodies access the CNS during periods of active inflammation that are associated with disruption of the blood-CSF barrier. CSF anti-Nfasc antibody titres correlated strongly with the release of NfL, suggesting that axonal injury could be related to the presence of Nfasc-specific antibodies. Following aHSCT, CSF NfL and NfH release were reduced without concomitant CSF anti-Nfasc antibody reductions, suggesting that the presence…

Subjects/Keywords: Multiple Sclerosis; gamma delta T-cell; neurofascin; neurofilament; antibody-dependent cellular cytotoxicity; antibody

11 more images…

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Black, J. (2015). Discerning the Mechanism of Gamma Delta T Cell-Mediated Damage in Multiple Sclerosis: the Potential Role of Antibodies in Disease Pathogenesis . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/31925

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Black, Jennifer. “Discerning the Mechanism of Gamma Delta T Cell-Mediated Damage in Multiple Sclerosis: the Potential Role of Antibodies in Disease Pathogenesis .” 2015. Thesis, University of Ottawa. Accessed January 16, 2021. http://hdl.handle.net/10393/31925.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Black, Jennifer. “Discerning the Mechanism of Gamma Delta T Cell-Mediated Damage in Multiple Sclerosis: the Potential Role of Antibodies in Disease Pathogenesis .” 2015. Web. 16 Jan 2021.

Vancouver:

Black J. Discerning the Mechanism of Gamma Delta T Cell-Mediated Damage in Multiple Sclerosis: the Potential Role of Antibodies in Disease Pathogenesis . [Internet] [Thesis]. University of Ottawa; 2015. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/10393/31925.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Black J. Discerning the Mechanism of Gamma Delta T Cell-Mediated Damage in Multiple Sclerosis: the Potential Role of Antibodies in Disease Pathogenesis . [Thesis]. University of Ottawa; 2015. Available from: http://hdl.handle.net/10393/31925

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Edinburgh

3. Zonta, Barbara. The Neurofascins orchestrate assembly and maintenance of axonal domains in the central nervous system.

Degree: PhD, 2008, University of Edinburgh

URL: http://hdl.handle.net/1842/3431

► Close interaction between oligodendrocytes and axons is essential to initiate myelination and to form specialised domains along myelinated fibres. These domains are characterised by the… (more)

▼ Close interaction between oligodendrocytes and axons is essential to initiate myelination and to form specialised domains along myelinated fibres. These domains are characterised by the assembly of protein complexes at the axon-glia interface and key components of these complexes are the Neurofascins. Neurofascins are transmembrane glycoproteins belonging to the L1 subgroup of the Immunoglobulin (Ig) superfamily of cell adhesion molecules. The Neurofascin (Nfasc) gene is subject to extensive alternative splicing. Two of the best characterised isoforms are Nfasc155 and Nfasc186, which are expressed in glia and neurons respectively. In myelinated fibres, Nfasc186 is the predominant isoform expressed at nodes of Ranvier and axon initial segments (AIS) in both the central and peripheral nervous system (CNS and PNS), whereas Nfasc155 resides on the glial side of the paranodal axoglial junction. The Neurofascin gene has been inactivated by homologous recombination and Neurofascin-null mice die within the first week of postnatal life. The main focus of this work was to investigate the role of the Neurofascins in the developing CNS. Similarly to what has been previously observed in the PNS, this study shows that in myelinated fibres of the spinal cord, nodal and paranodal markers are mislocalised and axoglial junctions do not form in the absence of the Neurofascins. In contrast to the PNS, where ensheathment of axons is unaffected, myelin proteins in the CNS are greatly reduced in the mutant. This appears to be due to the reduced ability of oligodendrocyte myelinating processes to extend along axons. This work also shows that the role of Nfasc186 is to maintain the long term stability of the AIS rather than its assembly. In the PNS, Nfasc186 was found to play an essential role in node assembly. However, PNS and CNS nodes are likely to assemble by different mechanisms. To investigate the relative contribution of the Neurofascin isoforms in CNS node assembly, this work made use of transgenic lines in which either neuronal Nfasc186 or glial Nfasc155 was expressed on a Neurofascin null background. Expression of either isoform was found to independently rescue the nodal complex and a model of how the Neurofascins cooperate in the assembly of the CNS node of Ranvier is proposed.

Subjects/Keywords: 612.8; neurofascin; myelination; nodes of ranvier

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zonta, B. (2008). The Neurofascins orchestrate assembly and maintenance of axonal domains in the central nervous system. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/3431

Chicago Manual of Style (16^th Edition):

Zonta, Barbara. “The Neurofascins orchestrate assembly and maintenance of axonal domains in the central nervous system.” 2008. Doctoral Dissertation, University of Edinburgh. Accessed January 16, 2021. http://hdl.handle.net/1842/3431.

MLA Handbook (7^th Edition):

Zonta, Barbara. “The Neurofascins orchestrate assembly and maintenance of axonal domains in the central nervous system.” 2008. Web. 16 Jan 2021.

Vancouver:

Zonta B. The Neurofascins orchestrate assembly and maintenance of axonal domains in the central nervous system. [Internet] [Doctoral dissertation]. University of Edinburgh; 2008. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/1842/3431.

Council of Science Editors:

Zonta B. The Neurofascins orchestrate assembly and maintenance of axonal domains in the central nervous system. [Doctoral Dissertation]. University of Edinburgh; 2008. Available from: http://hdl.handle.net/1842/3431

University of St. Andrews

4. Herron, Lissa Rocha. A study of the behaviour and interactions of the novel FERM protein Willin .

Degree: 2008, University of St. Andrews

URL: http://hdl.handle.net/10023/418

► Willin is a novel member of the Four-point-one Ezrin Radixin Moesin (FERM) protein superfamily, containing an N-terminal FERM domain most like the Ezrin-Radixin-Moesin (ERM) family… (more)

Subjects/Keywords: Willin; FERM; Merlin; Ezrin; Radixin; Moesin; Neurofascin; L1

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Herron, L. R. (2008). A study of the behaviour and interactions of the novel FERM protein Willin . (Thesis). University of St. Andrews. Retrieved from http://hdl.handle.net/10023/418

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Herron, Lissa Rocha. “A study of the behaviour and interactions of the novel FERM protein Willin .” 2008. Thesis, University of St. Andrews. Accessed January 16, 2021. http://hdl.handle.net/10023/418.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Herron, Lissa Rocha. “A study of the behaviour and interactions of the novel FERM protein Willin .” 2008. Web. 16 Jan 2021.

Vancouver:

Herron LR. A study of the behaviour and interactions of the novel FERM protein Willin . [Internet] [Thesis]. University of St. Andrews; 2008. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/10023/418.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Herron LR. A study of the behaviour and interactions of the novel FERM protein Willin . [Thesis]. University of St. Andrews; 2008. Available from: http://hdl.handle.net/10023/418

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Virginia Commonwealth University

5. Pomicter, Anthony. Discovery and Initial Characterizations of Neurofascin 155 High and Neurofascin 155 Low.

Degree: MS, Anatomy & Neurobiology, 2008, Virginia Commonwealth University

URL: https://doi.org/10.25772/FXZS-VR58 ; https://scholarscompass.vcu.edu/etd/1939

► This thesis contains the findings from four years of research regarding an oligodendrocyte protein named neurofascin 155. The role of this protein in maintaining adhesion… (more)

Subjects/Keywords: neurofascin; sulfatide; myelin; oligodendrocytes; paranode; Anatomy; Medicine and Health Sciences; Nervous System

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pomicter, A. (2008). Discovery and Initial Characterizations of Neurofascin 155 High and Neurofascin 155 Low. (Thesis). Virginia Commonwealth University. Retrieved from https://doi.org/10.25772/FXZS-VR58 ; https://scholarscompass.vcu.edu/etd/1939

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Pomicter, Anthony. “Discovery and Initial Characterizations of Neurofascin 155 High and Neurofascin 155 Low.” 2008. Thesis, Virginia Commonwealth University. Accessed January 16, 2021. https://doi.org/10.25772/FXZS-VR58 ; https://scholarscompass.vcu.edu/etd/1939.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Pomicter, Anthony. “Discovery and Initial Characterizations of Neurofascin 155 High and Neurofascin 155 Low.” 2008. Web. 16 Jan 2021.

Vancouver:

Pomicter A. Discovery and Initial Characterizations of Neurofascin 155 High and Neurofascin 155 Low. [Internet] [Thesis]. Virginia Commonwealth University; 2008. [cited 2021 Jan 16]. Available from: https://doi.org/10.25772/FXZS-VR58 ; https://scholarscompass.vcu.edu/etd/1939.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Pomicter A. Discovery and Initial Characterizations of Neurofascin 155 High and Neurofascin 155 Low. [Thesis]. Virginia Commonwealth University; 2008. Available from: https://doi.org/10.25772/FXZS-VR58 ; https://scholarscompass.vcu.edu/etd/1939

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Freie Universität Berlin

6. Diederich, Jan Markus. Antigen-specific T Cell response pattern in chronic inflammatory demyelinating polyneuropathy subtypes.

Degree: 2019, Freie Universität Berlin

URL: http://dx.doi.org/10.17169/refubium-25888

► Abstract Background Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare autoimmune disorder of the peripheral nervous system and can be divided into typical CIDP and… (more)

▼ Abstract Background Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare autoimmune disorder of the peripheral nervous system and can be divided into typical CIDP and atypical CIDP manifestations. Atypical variants are among others distal acquired demyelinating polyneuropathy (DADS), multifocal acquired demyelinating sensory and motor polyneuropathy (MADSAM), and sensory CIDP. Differentiating these variants from one another and from non-immune polyneuropathies remains challenging in clinical neurology. T-cell responses to a range of different myelin-derived epitopes were detected in patients with CIDP. Further, the association of distinct clinical phenotypes of CIDP with specific neurofascin-autoantibodies in patient´s blood sera was shown. Based on these findings I hypothesize, that CIDP-variants differ in their specific immunoreaction against different epitopes of the peripheral nervous system. In order to proof that hypothesis, the objective of this study is to investigate whether different subtypes of CIDP show specifications in their type 1 helper T cell (TH1) responses against paranodal and nodal neurofascin (NF155 and NF186), as well as myelin-specific peptides myelin protein zero (P0 180–199) and myelin basic protein (MBP 82–100). Further, I investigate if in association to TH1-reactions against NF155 and NF186 autoantibodies against these epitopes can be detected. Methods Interferon-gamma enzyme-linked immunospot assay was used to detect antigen-specific TH1-responses in 48 patients with diagnosed typical CIDP (n=18), DADS (n=8), MADSAM (n=9), and sensory CIDP (n=13) compared to other non-immune polyneuropathy (ON, n=19) and healthy controls (HC, n=9). Blood sera of these patients were tested for autoantibodies against NF155 and NF 186 with an enzyme-linked immunosorbent assay. Results Positive TH1-responses against two or more antigens were highly predictive for CIDP (positive predictive value = 0.95) and were found in 77% of CIDP patients. Compared to controls, MADSAM and sensory CIDP patients showed broadest TH1-responses to all four antigens. The area under the receiver operating characteristics curve (AUC) of NF186 in MADSAM was 0.94 [95% confidential interval (CI) 0.82–1] compared to ON. For sensory CIDP, AUC of P0 180–199 was 0.94 [95% CI 0.86–1] and for MBP 82–100 0.95 [95% CI 0.88–1] compared to ON. Autoantibodies against NF155 or NF186 were not detected. Conclusion TH1-responses to investigated paranodal, nodal and myelin-specific peptides are common in CIDP. TH1-reactions against NF186 may be used as biomarker for MADSAM and TH1-reactions against P0 180–199 and MBP 82–100 as biomarkers for sensory CIDP. Larger multicenter studies are necessary to establish these biomarkers as diagnostic tools. Advisors/Committee Members: unknown (gender), N.N. (firstReferee), N.N. (furtherReferee).

Subjects/Keywords: CIDP; Neurofascin; Chronic inflammatory demyelinating polyneuropathy; NF; MBP; myelin; P0; ELISPOT; T cell; 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Diederich, J. M. (2019). Antigen-specific T Cell response pattern in chronic inflammatory demyelinating polyneuropathy subtypes. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-25888

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Diederich, Jan Markus. “Antigen-specific T Cell response pattern in chronic inflammatory demyelinating polyneuropathy subtypes.” 2019. Thesis, Freie Universität Berlin. Accessed January 16, 2021. http://dx.doi.org/10.17169/refubium-25888.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Diederich, Jan Markus. “Antigen-specific T Cell response pattern in chronic inflammatory demyelinating polyneuropathy subtypes.” 2019. Web. 16 Jan 2021.

Vancouver:

Diederich JM. Antigen-specific T Cell response pattern in chronic inflammatory demyelinating polyneuropathy subtypes. [Internet] [Thesis]. Freie Universität Berlin; 2019. [cited 2021 Jan 16]. Available from: http://dx.doi.org/10.17169/refubium-25888.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Diederich JM. Antigen-specific T Cell response pattern in chronic inflammatory demyelinating polyneuropathy subtypes. [Thesis]. Freie Universität Berlin; 2019. Available from: http://dx.doi.org/10.17169/refubium-25888

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

		in
And / Or
		in
And / Or
		in
And / Or
		in

Open Access Theses and Dissertations