Afferent Visual Pathway Affection in Patients with PMP22 Deletion-Related Hereditary Neuropathy with Liability to Pressure Palsies

Brandt, Alexander U.; Meinert-Bohn, Elena; Rinnenthal, Jan Leo; Zimmermann, Hanna; Mikolajczak, Janine; Oberwahrenbrock, Timm; Papazoglou, Sebastian; Pfüller, Caspar; Schinzel, Johann; Tackenberg, Björn; Paul, Friedemann; Hahn, Katrin; Bellmann‐Strobl, Judith

doi:10.1371/journal.pone.0164617

Cited by 6 publications

(4 citation statements)

References 39 publications

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“…Pyramidal signs were described by Thomas et al (1997) [ 93 ] in three CMT1A (triploidy of pmp22) patients and Chanson et al (2013) [ 94 ], reported a reduction of white matter volume and cognitive impairment in 70% of CMT1A studied patients. More recently, Brandt et al (2016) [ 95 ] have also described functional, metabolic, and macrostructural alterations in the afferent visual system in eighteen patients with HNPP (pmp22 haploidy). Taking together these previous findings, they further provide some understanding related to the general role of pmp22 expression, especially in the CNS, as well as to normal gene copy number (genic dosage effect).…”

Section: Discussionmentioning

confidence: 99%

Central Alteration in Peripheral Neuropathy of Trembler-J Mice: Hippocampal pmp22 Expression and Behavioral Profile in Anxiety Tests

et al. 2021

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Charcot–Marie–Tooth (CMT) type 1 disease is the most common human hereditary demyelinating neuropathy. Mutations in pmp22 cause about 70% of all CMT1. Trembler-J (TrJ/+) mice are an animal model of CMT1E, having the same spontaneous pmp22 mutation that is found in humans. We compared the behavior profile of TrJ/+ and +/+ (wild-type) in open-field and elevated-plus-maze anxiety tests. In these tests, TrJ/+ showed an exclusive head shake movement, a lower frequency of rearing, but a greater frequency of grooming. In elevated-plus-maze, TrJ/+ defecate more frequently, performed fewer total entries, and have fewer entries to closed arms. These hippocampus-associated behaviors in TrJ/+ are consistent with increased anxiety levels. The expression of pmp22 and soluble PMP22 were evaluated in E17-hippocampal neurons and adult hippocampus by in situ hybridization and successive immunohistochemistry. Likewise, the expression of pmp22 was confirmed by RT-qPCR in the entire isolated hippocampi of both genotypes. Moreover, the presence of aggregated PMP22 was evidenced in unmasked granular hippocampal adult neurons and shows genotypic differences. We showed for the first time a behavior profile trait associated with anxiety and a differential expression of pmp22/PMP22 in hippocampal neurons of TrJ/+ and +/+ mice, demonstrating the involvement at the central level in an animal model of peripheral neuropathy (CMT1E).

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Section: Discussionmentioning

confidence: 99%

Central Alteration in Peripheral Neuropathy of Trembler-J Mice: Hippocampal pmp22 Expression and Behavioral Profile in Anxiety Tests

et al. 2021

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“…Currently, OCT finds broad applicability in ophthalmology and dermatology, and more recently, in neurology . With our present study, we account for the increasing interest in rheumatology to employ OCT in diagnosis and drug monitoring by repeatedly visualizing cartilage degeneration.…”

Section: Discussionmentioning

confidence: 99%

Coregistered Spectral Optical Coherence Tomography and Two‐Photon Microscopy for Multimodal Near‐Instantaneous Deep‐Tissue Imaging

et al. 2020

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Two-photon microscopy (2PM) has brought unique insight into the mechanisms underlying immune system dynamics and function since it enables monitoring of cellular motility and communication in complex systems within their genuine environment-the living organism. However, use of 2PM in clinical settings is limited. In contrast, optical coherence tomography (OCT), a noninvasive label-free diagnostic imaging method, which allows monitoring morphologic changes of large tissue regions in vivo, has found broad application in the clinic. Here we developed a combined multimodal technology to achieve near-instantaneous coregistered OCT, 2PM, and second harmonic generation (SHG) imaging over large volumes (up to 1,000 × 1,000 × 300 μm 3 ) of tendons and other tissue compartments in mouse paws, as well as in mouse lymph nodes, spleens, and femurs. Using our multimodal imaging approach, we found differences in macrophage cell shape and motility behavior depending on whether they are located in tendons or in the surrounding tissue compartments of the mouse paw. The cellular shape of tissue-resident macrophages, indicative for their role in tissue, correlated with the supramolecular organization of collagen as revealed by SHG and OCT. Hence, the herepresented approach of coregistered OCT and 2PM has the potential to link specific cellular phenotypes and functions (as revealed by 2PM) to tissue morphology (as highlighted by OCT) and thus, to build a bridge between basic research knowledge and clinical observations.

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“…The PMP22 gene is mainly expressed in the peripheral nervous system (PNS); however, mRNA and protein can also be found in the central nervous system (CNS) (18). Recent studies suggested the important involvement of the CNS in most patients with PMP22 deletion (18, 19). This is supported by prolonged latencies of visual evoked potentials, neurochemical alterations with decreased N -acetylaspartate (NAA) and creatine (Cre) concentrations, white matter (WM) volume reduction detected by cMRI, cognitive impairment (in 70% of patients), and fractional anisotropy alteration in several WM regions (e.g., in the columns of the fornix) (18–20).…”

Section: Discussionmentioning

confidence: 99%

Schizophrenia and Hereditary Polyneuropathy: PMP22 Deletion as a Common Pathophysiological Link?

et al. 2019

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Background: Schizophrenic disorders are common and debilitating due to their symptoms, which can include delusions, hallucinations, and other negative symptoms. Organic forms can result from various cerebral disorders. In this paper, we discuss a potential association between schizophrenia and hereditary polyneuropathies (PNPs). Case presentation: We present the case of a 55-year-old female patient with chronically paranoid–hallucinatory schizophrenia, severe cognitive deficits since the age of 30, and comorbid repeated focal pressure neuropathies beginning at age 20. At the age of 35, genetic testing revealed a deletion on chromosome 17p12 covering the peripheral myelin protein 22 gene ( PMP22 ), which led to the diagnosis of hereditary neuropathy with liability to pressure palsy (HNPP). Cerebral magnetic resonance imaging showed internal atrophy, magnetic resonance spectroscopy found alteration of the glutamate and myo-inositol levels in the anterior cingulate cortex, neuropsychological testing showed deficits in working memory and psychomotor speed, and electrophysiological testing detected signs of sensorimotor demyelinating PNP (accentuated in the legs). Conclusion: There may be an association between schizophrenia and HNPP. In observational studies, the deletion of interest (chromosome 17p12) was nearly 10 times more common in schizophreniform patients than in controls. This potential association could be pathophysiologically explained by the role of PMP22, which is mainly expressed in the peripheral nervous system. However, PMP22 mRNA and protein can also be found in the brain. PMP22 seems to play an important role in regulating cell growth and myelination, functions that are disturbed in schizophrenia. Such a connection obviously cannot be clarified on the basis of one case. Future studies should analyze whether patients with HNPP exhibit increased rates of psychotic disorders, and patients with schizophrenia and repeated focal pressure neuropathies should be examined for the PMP22 mutation. Alternatively, the co-occurrence of schizophrenia and HNPP could be coincidental.

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Afferent Visual Pathway Affection in Patients with PMP22 Deletion-Related Hereditary Neuropathy with Liability to Pressure Palsies

Cited by 6 publications

References 39 publications

Central Alteration in Peripheral Neuropathy of Trembler-J Mice: Hippocampal pmp22 Expression and Behavioral Profile in Anxiety Tests

Central Alteration in Peripheral Neuropathy of Trembler-J Mice: Hippocampal pmp22 Expression and Behavioral Profile in Anxiety Tests

Coregistered Spectral Optical Coherence Tomography and Two‐Photon Microscopy for Multimodal Near‐Instantaneous Deep‐Tissue Imaging

Schizophrenia and Hereditary Polyneuropathy: PMP22 Deletion as a Common Pathophysiological Link?

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