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Goepfert, M.

Publications and source records attributed to Goepfert, M..

2 recordsLinked to original sources

Axon demyelination and degeneration in a zebrafishspastizin model of hereditary spastic paraplegia

Hereditary spastic paraplegias (HSPs) are a diverse set of neurological disorders characterized by progressive spasticity and weakness in the lower limbs caused by damage to the axons of the corticospinal tract. More than 88 genetic mutations have been associated with HSP, yet the mechanisms underlying these disorders are little understood. We studied the pathogenesis of one form of HSP known as spastic paraplegia 15 (SPG15). This disorder is caused by mutations in the ZFYVE26 gene, which codes for a protein called SPASTIZIN. We show that, in zebrafish, the significant reduction of Spastizin caused degeneration of Mauthner (M)-cells. M-cell degeneration is associated with axon demyelination in the spinal cord and impaired locomotion in the spastizin mutants. Our findings reveal that the mutation not only compromises axonal integrity but also affects the structural molecules of the myelin sheath, laying the foundation for degeneration and advancing our understanding of the intricate mechanisms underlying HSPs.

neuroscience↗

Renal and Renal Sinus Fat Volumes as Quantified by Magnetic Resonance Imaging in Subjects with Prediabetes, Diabetes, and Normal Glucose Tolerance.

PurposeThe aim of this study was to assess the volume of the respective kidney compartments with particular interest in renal sinus fat as an early biomarker and to compare the distribution between individuals with normal glucose levels and individuals with prediabetes and diabetes.\n\nMaterial and MethodsThe sample comprised N = 366 participants who were either normoglycemic (N = 230), had prediabetes (N = 87) or diabetes (N =49), as determined by Oral Glucose Tolerance Test. Other covariates were obtained by standardized measurements and interviews. Whole-body MR measurements were performed on a 3 Tesla scanner. For assessment of the kidneys, a coronal T1w dual-echo Dixon and a coronal T2w single shot fast spin echo sequence were employed. Stepwise semi-automated segmentation of the kidneys on the Dixon-sequences was based on thresholding and geometric assumptions generating volumes for the kidneys and sinus fat. Inter- and intra-reader variability were determined on a subset of 40 subjects. Associations between glycemic status and renal volumes were evaluated by linear regression models, adjusted for other potential confounding variables. Furthermore, the association of renal volumes with visceral adipose tissue was assessed by linear regression models and Pearsons correlation coefficient.\n\nResultsRenal volume, renal sinus volume and renal sinus fat increased gradually from normoglycemic controls to individuals with prediabetes to individuals with diabetes (renal volume: 280.3{+/-}64.7 ml vs 303.7{+/-}67.4 ml vs 320.6{+/-}77.7ml, respectively, p < 0.001). After adjustment for age and sex, prediabetes and diabetes were significantly associated to increased renal volume, sinus volume (e.g. {beta}prediabetes = 10.1, 95% CI: [6.5, 13.7]; p<0.01, {beta}Diabetes = 11.86, 95% CI: [7.2, 16.5]; p<0.01) and sinus fat (e.g. {beta}prediabetes = 7.13, 95% CI: [4.5, 9.8]; p<0.001, {beta}Diabetes = 7.34, 95% CI: [4.0, 10.7]; p<0.001). Associations attenuated after adjustment for additional confounders were only significant for prediabetes and sinus volume ({beta} =4.0 95% CI [0.4, 7.6]; p<0.05). Hypertension was significantly associated with increased sinus volume ({beta} = 3.7, 95% CI: [0.4, 6.9; p<0.05]) and absolute sinus fat volume ({beta} = 3.0, 95%CI: [0.7, 5.2]; p<0.05). GFR and all renal volumes were significantly associated as well as urine albumin levels and renal sinus volume ({beta} = 1.6, 95% CI: [0.2, 3.0]; p<0.05). There was a highly significant association between VAT and the absolute sinus fat volume ({beta} = 2.75, 95% CI: [2.3, 3.2]; p<0.01).\n\nConclusionRenal volume and particularly renal sinus fat volume already increases significantly in prediabetic subjects. There is a significant association between VAT and renal sinus fat, suggesting that there are metabolic interactions between these perivascular fat compartments.

epidemiology↗