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Biomedicines
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Central and Peripheral Nervous Systems: Structure, Function, and Diseases
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Central and Peripheral Nervous Systems: Structure, Function, and Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 11944

Special Issue Editors

Dr. Andre Huss

E-Mail Website
Guest Editor
Department of Neurology, University Hospital Ulm, 89081 Ulm, Germany
Interests: biomarker; cerebrospinal fluid; neurodegeneration; neuroinflammation
Prof. Dr. Hayrettin Tumani

E-Mail Website
Co-Guest Editor
Department of Neurology, Ulm University, Oberer Eselsberg 45, 89081 Ulm, Germany
Interests: blood-CSF barrier function; process-specific biomarker; cerebrospinal fluid; neuroinflammation; neurodegeneration

Special Issue Information

Dear Colleagues,

This Special Collection aims at providing new insights into the mechanisms of the central and peripheral nervous systems. This includes all research projects that address general neurochemical mechanisms (structural and functional) in health and diseases. One main interest of this collection is to differentiate mechanisms that are specific for the CNS and PNS. This may include through data from cell culture, mouse models, and human subjects (biomarker analyses or immunohistochemistry of brain tissue), so long as there is a clear translational level for the enlightenment of molecular mechanisms in health and disease that are of particular interest in neurology. In particular, mechanisms of neurodegeneration, neuroinflammation, demyelination, and impairment of the blood-brain barrier are of specific interest. Biomarker analyses may include examination of cerebrospinal fluid (CSF), serum, plasma, or other suitable specimens, and we welcome all kinds of promising types of biomarkers (protein, DNA, RNA, imaging, etc.). We encourage all colleagues who are working within this highly interesting research field to participate in this Special Collection.

Dr. Andre Huss
Prof. Dr. Hayrettin Tumani
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • CNS
  • PNS
  • biomarker
  • neurodegeneration
  • axonal damage
  • neuroinflammation
  • demyelination
  • BBB
  • CSF

Published Papers (6 papers)

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Research

22 pages, 4720 KiB  
Article
Compromised Myelin and Axonal Molecular Organization Following Adult-Onset Sulfatide Depletion
by Elizabeth Dustin, Edna Suarez-Pozos, Camryn Stotesberry, Shulan Qiu, Juan Pablo Palavicini, Xianlin Han and Jeffrey L. Dupree
Biomedicines 2023, 11(5), 1431; https://doi.org/10.3390/biomedicines11051431 - 12 May 2023
Cited by 3 | Viewed by 1670
Abstract
3-O-sulfogalactosylceramide, or sulfatide, is a prominent myelin glycosphingolipid reduced in the normal appearing white matter (NAWM) in Multiple Sclerosis (MS), indicating that sulfatide reduction precedes demyelination. Using a mouse model that is constitutively depleted of sulfatide, we previously demonstrated that sulfatide is essential [...] Read more.
3-O-sulfogalactosylceramide, or sulfatide, is a prominent myelin glycosphingolipid reduced in the normal appearing white matter (NAWM) in Multiple Sclerosis (MS), indicating that sulfatide reduction precedes demyelination. Using a mouse model that is constitutively depleted of sulfatide, we previously demonstrated that sulfatide is essential during development for the establishment and maintenance of myelin and axonal integrity and for the stable tethering of certain myelin proteins in the sheath. Here, using an adult-onset depletion model of sulfatide, we employ a combination of ultrastructural, immunohistochemical and biochemical approaches to analyze the consequence of sulfatide depletion from the adult CNS. Our findings show a progressive loss of axonal protein domain organization, which is accompanied by axonal degeneration, with myelin sparing. Similar to our previous work, we also observe differential myelin protein anchoring stabilities that are both sulfatide dependent and independent. Most notably, stable anchoring of neurofascin155, a myelin paranodal protein that binds the axonal paranodal complex of contactin/Caspr1, requires sulfatide. Together, our findings show that adult-onset sulfatide depletion, independent of demyelination, is sufficient to trigger progressive axonal degeneration. Although the pathologic mechanism is unknown, we propose that sulfatide is required for maintaining myelin organization and subsequent myelin–axon interactions and disruptions in these interactions results in compromised axon structure and function. Full article
(This article belongs to the Special Issue Central and Peripheral Nervous Systems: Structure, Function, and Diseases)
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15 pages, 921 KiB  
Article
Neural Signatures of Error Processing in Depressed Adolescents with Comorbid Non-Suicidal Self-Injury (NSSI)
by Kathrin Malejko, Stefan Hafner, Rebecca C. Brown, Paul L. Plener, Georg Grön, Heiko Graf and Birgit Abler
Biomedicines 2022, 10(12), 3188; https://doi.org/10.3390/biomedicines10123188 - 8 Dec 2022
Cited by 1 | Viewed by 1474
Abstract
Non-suicidal self-injury (NSSI), as a highly prevalent psychiatric symptom in adolescents and young adults, is defined as the deliberate destruction of body tissue without suicidal intent. Impulsivity and dysfunctional response inhibition have been suggested to play a central role in adolescents’ vulnerability to [...] Read more.
Non-suicidal self-injury (NSSI), as a highly prevalent psychiatric symptom in adolescents and young adults, is defined as the deliberate destruction of body tissue without suicidal intent. Impulsivity and dysfunctional response inhibition have been suggested to play a central role in adolescents’ vulnerability to self-harm. To investigate the potentially distinct neurobiology of NSSI, we used a well-established Go/No Go task in which activation of the inferior frontal gyrus (IFG) and dorsal anterior cingulate cortex (dACC) is interpreted as a neural correlate of processing failed response inhibition. Task-based functional magnetic resonance imaging data were obtained from 14 adolescents with a diagnosis of major depression and a history of NSSI (MD-NSSI), 13 depressed adolescents without NSSI (MD-only), and 14 healthy controls (HC). In line with hypotheses of dysfunctional response inhibition, we observed increased rates of commission errors in MD-NSSI along with significantly reduced error-related activations of the dACC and IFG. Intact response inhibition, as reflected by low commission error rates not different from HC, was observed in MD-only, along with increased activation of the error-processing network. Our findings support the hypothesis of a distinct neurobiological signature of NSSI. Further research on biomarkers of NSSI could focus on behavioral and neural correlates of failed response inhibition. Full article
(This article belongs to the Special Issue Central and Peripheral Nervous Systems: Structure, Function, and Diseases)
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10 pages, 852 KiB  
Article
The TRACK-MS Test Battery: A Very Brief Tool to Track Multiple Sclerosis-Related Cognitive Impairment
by Daniela Taranu, Hayrettin Tumani, Jill Holbrook, Visal Tumani, Ingo Uttner and Patrick Fissler
Biomedicines 2022, 10(11), 2975; https://doi.org/10.3390/biomedicines10112975 - 18 Nov 2022
Cited by 5 | Viewed by 2278
Abstract
Tracking cognition in patients with multiple sclerosis (MS) is important for detection of disease progression but it is often not performed in routine settings due to time constraints. This exploratory cohort study aims to develop a very brief repeatable tracking tool with comparable [...] Read more.
Tracking cognition in patients with multiple sclerosis (MS) is important for detection of disease progression but it is often not performed in routine settings due to time constraints. This exploratory cohort study aims to develop a very brief repeatable tracking tool with comparable test quality criteria to the current gold standard, the Brief International Cognitive Assessment for MS (BICAMS). The study included 88 participants (22 healthy controls, 66 MS patients) who were examined at baseline and at one-year follow-up. As a validity criterion for the six administered cognitive tests, we assessed the difference between MS patients and HC, and the correlation with MS-related disability. Combining the two tests with the highest validity—the Controlled Oral Word Association Test and Symbol Digit Modalities Test—yielded an administration time of 5 min. Comparing this new TRACK-MS test battery with the 15 min BICAMS indicated that TRACK-MS showed larger differences between MS patients and healthy controls, a higher correlation with MS-related disability, smaller practice effects, and a good test–retest reliability. We provide evidence that TRACK-MS, although faster to administer, showed at least comparable quality criteria as the BICAMS. As the study was exploratory, replication of these results is necessary. Full article
(This article belongs to the Special Issue Central and Peripheral Nervous Systems: Structure, Function, and Diseases)
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12 pages, 2409 KiB  
Article
Saliva Free Light Chains in Patients with Neuro-Sjögren
by Franz Felix Konen, Tabea Seeliger, Philipp Schwenkenbecher, Stefan Gingele, Konstantin Fritz Jendretzky, Kurt-Wolfram Sühs, Diana Ernst, Torsten Witte and Thomas Skripuletz
Biomedicines 2022, 10(10), 2470; https://doi.org/10.3390/biomedicines10102470 - 3 Oct 2022
Cited by 1 | Viewed by 1844
Abstract
Background: Sjögren’s syndrome (SS) is an autoimmune disease characterized by sicca symptoms and various extra-glandular manifestations. The diagnosis of SS requires sicca symptoms, anti-SSA(Ro)-antibody positivity, and/or pathological focus scores on a minor salivary gland biopsy. Previous studies have investigated different biomarkers in order [...] Read more.
Background: Sjögren’s syndrome (SS) is an autoimmune disease characterized by sicca symptoms and various extra-glandular manifestations. The diagnosis of SS requires sicca symptoms, anti-SSA(Ro)-antibody positivity, and/or pathological focus scores on a minor salivary gland biopsy. Previous studies have investigated different biomarkers in order to avoid invasive diagnostic procedures. It was found that kappa and lambda free light chains (KFLC and LFLC) in saliva are specific for SS. Methods: FLC concentrations in saliva and serum were determined in 130 patients—50 with SS and neurological involvement (Neuro-Sjögren) and 80 neurological controls. The EULAR SS disease activity index and patient reported index (ESSPRI) were determined in patients with SS. Results: Patients with SS revealed increased pain and decreased saliva production according to the ESSPRI and Saxon test, respectively, with increasing FLC concentrations in the saliva. No significant differences in serum and salivary protein concentrations were observed between patients with SS and controls. Conclusion: KFLC and LFLC concentrations in saliva are not suitable to distinguish patients with Neuro-Sjögren and neurological control subjects, thus a diagnostic biopsy is still required. The association of salivary KFLC and LFLC concentrations with saliva production and ESSPRI pain score suggests a complex relationship between dryness and pain in patients with SS. Full article
(This article belongs to the Special Issue Central and Peripheral Nervous Systems: Structure, Function, and Diseases)
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7 pages, 407 KiB  
Communication
Evidence for an Intrathecal Immunoglobulin Synthesis by Kappa Free Light Chains in Neurological Patients with an Isolated Band in Isoelectric Focusing
by Bastian Weiss, Alexander Pichler, Anna Damulina, Arabella Buchmann, Sonja Hochmeister, Thomas Seifert-Held, Christian Enzinger, Juan-Jose Archelos and Michael Khalil
Biomedicines 2022, 10(9), 2202; https://doi.org/10.3390/biomedicines10092202 - 6 Sep 2022
Cited by 1 | Viewed by 1554
Abstract
The gold standard for detecting intrathecal immunoglobulin synthesis is the determination of the oligoclonal band (OCB) in the cerebrospinal fluid (CSF) using isoelectric focusing (IEF). Controversy still exists regarding the significance of an isolated band in the CSF. A highly promising alternative method [...] Read more.
The gold standard for detecting intrathecal immunoglobulin synthesis is the determination of the oligoclonal band (OCB) in the cerebrospinal fluid (CSF) using isoelectric focusing (IEF). Controversy still exists regarding the significance of an isolated band in the CSF. A highly promising alternative method for the assessment of intrathecal inflammation is the quantification of kappa free light chains (k-FLC). Our aim was to evaluate the clinical significance of quantitative k-FLC in patients with an isolated band in the CSF. Using the Human Kappa Freelite Mx Kit on a turbidimetric Optilite®, we quantified the k-FLCs in paired CSF and serum samples in 47 patients with a single band in IEF. We classified patients into 27× inflammatory neurological disorders (IND), 2× peripheral inflammatory neurological disorders (PIND), 9× non-inflammatory neurological disorders (NIND) and 9× symptomatic controls (SC) based on their medical diagnosis. k-FLC were below the lower measurement limit of the analyser (LML) in all SC and PIND, as well as in 8 out of 9 NIND and 11 IND. Only 1 NIND and 16 IND were above the LML, and of these, only 14 IND were above the upper discrimination limit (Qlim). A neuroinflammatory nature of the diseases can be indicated in many cases by positive k-FLC in patients with an isolated band in IEF. The measurement of k-FLC can support the diagnosis of neurological diseases if they are included in the routine work-up. Full article
(This article belongs to the Special Issue Central and Peripheral Nervous Systems: Structure, Function, and Diseases)
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15 pages, 4597 KiB  
Article
Association of Serum GFAP with Functional and Neurocognitive Outcome in Sporadic Small Vessel Disease
by André Huss, Ahmed Abdelhak, Benjamin Mayer, Hayrettin Tumani, Hans-Peter Müller, Katharina Althaus, Jan Kassubek, Markus Otto, Albert C. Ludolph, Deniz Yilmazer-Hanke and Hermann Neugebauer
Biomedicines 2022, 10(8), 1869; https://doi.org/10.3390/biomedicines10081869 - 2 Aug 2022
Cited by 10 | Viewed by 2564
Abstract
Cerebrospinal fluid (CSF) and serum biomarkers are critical for clinical decision making in neurological diseases. In cerebral small vessel disease (CSVD), white matter hyperintensities (WMH) are an important neuroimaging biomarker, but more blood-based biomarkers capturing different aspects of CSVD pathology are needed. In [...] Read more.
Cerebrospinal fluid (CSF) and serum biomarkers are critical for clinical decision making in neurological diseases. In cerebral small vessel disease (CSVD), white matter hyperintensities (WMH) are an important neuroimaging biomarker, but more blood-based biomarkers capturing different aspects of CSVD pathology are needed. In 42 sporadic CSVD patients, we prospectively analysed WMH on magnetic resonance imaging (MRI) and the biomarkers neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), chitinase3-like protein 1 (CHI3L1), Tau and Aβ1-42 in CSF and NfL and GFAP in serum. GFAP and CHI3L1 expression was studied in post-mortem brain tissue in additional cases. CSVD cases with higher serum NfL and GFAP levels had a higher modified Rankin Scale (mRS) and NIHSS score and lower CSF Aβ1-42 levels, whereas the CSF NfL and CHI3L1 levels were positively correlated with the WMH load. Moreover, the serum GFAP levels significantly correlated with the neurocognitive functions. Pathological analyses in CSVD revealed a high density of GFAP-immunoreactive fibrillary astrocytic processes in the periventricular white matter and clusters of CHI3L1-immunoreactive astrocytes in the basal ganglia and thalamus. Thus, besides NfL, serum GFAP is a highly promising fluid biomarker of sporadic CSVD, because it does not only correlate with the clinical severity but also correlates with the cognitive function in patients. Full article
(This article belongs to the Special Issue Central and Peripheral Nervous Systems: Structure, Function, and Diseases)
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