Ultrastructural characterization of mitochondrial damage in experimental autoimmune neuritis

Muke, Ines; Sprenger, Alina; Bobylev, Ilja; Wiemer, Valerie M.; Barham, Mohammed; Neiss, Wolfram F.; Lehmann, Helmar C.

doi:10.1016/j.jneuroim.2020.577218

Cited by 5 publications

(3 citation statements)

References 36 publications

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“…Serum NfL has been reported to be a useful biomarker reflecting axonal damage in CIDP. 18, 37 In the present study, the serum NfL levels were discovered to be negatively correlated with CMAP amplitude in the nerves within the upper and lower limbs, possibly revealing axonal degeneration. An increase in serum NfL was confirmed to be associated with disease progression 1 year after serum sampling in patients with CIDP but has not been shown to reflect short-term treatment responses after IVIg administration.…”

Section: Discussionsupporting

confidence: 50%

“…15, 16 During the process of demyelination, the dysfunction of mitochondria occurs, leading to aggravated oxidative stress. 17, 18 Consequently, a shift from aerobic to anaerobic metabolism occurs, depleting the hexosamine pathway. As a result, the biosynthesis of uridine diphosphate-GlcNAc, the precursor of N -glycans branching, is hindered.…”

Section: Introductionmentioning

confidence: 99%

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Serum Glycobiomarkers Defining Therapeutic Response to Intravenous Immunoglobulin in Chronic Inflammatory Demyelinating Polyneuropathy

Furukawa,

Fukami,

Hanamatsu

et al. 2024

Preprint

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Background Glycosylation plays a crucial role in various pathologic conditions, including inflammation. This study conducted a comprehensive glycan analysis of serum to determine how glycan biomarkers are associated with the pathophysiology of chronic inflammatory demyelinating polyneuropathy (CIDP) and the effects of its treatment. Methods We comparatively analyzedN- andO-glycans in the pretreatment serum of 27 treatment-naïve patients with typical CIDP and age- and sex-matched 20 healthy controls (HC) using mass spectrometry. We determined the association between clinical parameters and glycans. Treatment response was defined according to the degree of improvement in the modified Rankin Scale 2 weeks after the first dose of intravenous immunoglobulin (IVIg), and the serum glycan and neurofilament light chain (NfL) levels were assessed at the baseline. Results Compared with the HC, the CIDP group demonstrated significantly lower levels of serum totalN–glycans (CIDP, median 973.3 [IQR 836.2-1131.3] pmol/µĹ; HC, 1125.0 [1005.0-1236.2] pmol/µĹ; p < 0.05), especially sialylatedN–glycans (CIDP, 898.0 [752.2-1037.2] pmol/µĹ; HC, 1064.4 [942.7-1189.8] pmol/µĹ; p < 0.01). In contrast, theO–glycan levels did not differ significantly between the two groups. Treatment response was associated with lowN–glycan levels but not with the serum NfL levels. For individual glycans, low levels of Hex2HexNAc2NeuAc2 [α2,6/α2,6] + Man3GlcNAc2, α2,6-linked sialylatedN–glycans, showed the treatment response group to have an area under the curve of 0.802 (p < 0.05).

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Section: Discussionsupporting

confidence: 50%

Section: Introductionmentioning

confidence: 99%

Serum Glycobiomarkers Defining Therapeutic Response to Intravenous Immunoglobulin in Chronic Inflammatory Demyelinating Polyneuropathy

Furukawa,

Fukami,

Hanamatsu

et al. 2024

Preprint

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“…The depolarized mitochondria in small diameter axons appeared to create a “plug” in the axon and even obstructed the traffick of other organelles ( Sajic et al, 2018 ). Schwann cell mitochondria have also been found to be morphologically and functionally altered as well ( Muke et al, 2020 ). These studies indicate that mitochondrial dysfunction is a common finding in preclinical and clinical studies on peripheral neuropathy.…”

Section: Hdac6 and Mitochondrial Dysfunction In Peripheral Neuropathymentioning

confidence: 99%

HDAC6: A Key Link Between Mitochondria and Development of Peripheral Neuropathy

English

Barton

2021

Front. Mol. Neurosci.

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Peripheral neuropathy, which is the result of nerve damage from lesions or disease, continues to be a major health concern due to the common manifestation of neuropathic pain. Most investigations into the development of peripheral neuropathy focus on key players such as voltage-gated ion channels or glutamate receptors. However, emerging evidence points to mitochondrial dysfunction as a major player in the development of peripheral neuropathy and resulting neuropathic pain. Mitochondrial dysfunction in neuropathy includes altered mitochondrial transport, mitochondrial metabolism, as well as mitochondrial dynamics. The mechanisms that lead to mitochondrial dysfunction in peripheral neuropathy are poorly understood, however, the Class IIb histone deacetylase (HDAC6), may play an important role in the process. HDAC6 is a key regulator in multiple mechanisms of mitochondrial dynamics and may contribute to mitochondrial dysregulation in peripheral neuropathy. Accumulating evidence shows that HDAC6 inhibition is strongly associated with alleviating peripheral neuropathy and neuropathic pain, as well as mitochondrial dysfunction, in in vivo and in vitro models of peripheral neuropathy. Thus, HDAC6 inhibitors are being investigated as potential therapies for multiple peripheral neuropathic disorders. Here, we review emerging studies and integrate recent advances in understanding the unique connection between peripheral neuropathy and mitochondrial dysfunction through HDAC6-mediated interactions.

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Antibiotics-Induced Intestinal Immunomodulation Attenuates Experimental Autoimmune Neuritis (EAN)

Sprenger-Svačina,

Klein,

Svačina

et al. 2024

J Neuroimmune Pharmacol

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Background The composition of gut microbiota plays a pivotal role in priming the immune system and thus impacts autoimmune diseases. Data on the effects of gut bacteria eradication via systemic antibiotics on immune neuropathies are currently lacking. This study therefore assessed the effects of antibiotics-induced gut microbiota alterations on the severity of experimental autoimmune neuritis (EAN), a rat model of Guillain-Barré Syndrome (GBS). Myelin P0 peptide 180–199 (P0 180–199)-induced EAN severity was compared between adult Lewis rats (12 weeks old) that received drinking water with or without antibiotics (colistin, metronidazole, vancomycin) and healthy rats, beginning antibiotics treatment immediately after immunization (day 0), and continuing treatment for 14 consecutive days. Neuropathy severity was assessed via a modified clinical score, and then related to gut microbiota alterations observed after fecal 16S rRNA gene sequencing at baseline and after EAN induction. Effectors of gut mucosal and endoneurial immunity were assessed via immunostaining. EAN rats showed increased gut mucosal permeability alongside increased mucosal CD8+ T cells compared to healthy controls. Antibiotics treatment alleviated clinical EAN severity and reduced endoneurial T cell infiltration, decreased gut mucosal CD8+ T cells and increased gut bacteria that may be associated with anti-inflammatory mechanisms, like Lactobacillus or Parasutterella. Our findings point out a relation between gut mucosal immunity and the pathogenesis of EAN, and indicate that antibiotics-induced intestinal immunomodulation might be a therapeutic approach to alleviate autoimmunity in immune neuropathies. Further studies are warranted to evaluate the clinical transferability of these findings to patients with GBS. Graphical Abstract

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Ultrastructural characterization of mitochondrial damage in experimental autoimmune neuritis

Cited by 5 publications

References 36 publications

Serum Glycobiomarkers Defining Therapeutic Response to Intravenous Immunoglobulin in Chronic Inflammatory Demyelinating Polyneuropathy

Serum Glycobiomarkers Defining Therapeutic Response to Intravenous Immunoglobulin in Chronic Inflammatory Demyelinating Polyneuropathy

HDAC6: A Key Link Between Mitochondria and Development of Peripheral Neuropathy

Antibiotics-Induced Intestinal Immunomodulation Attenuates Experimental Autoimmune Neuritis (EAN)

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