Dataset Information

A Drosophila model of the neurological symptoms in Mpv17-related diseases.

ABSTRACT: Mutations in the Mpv17 gene are responsible for MPV17-related hepatocerebral mitochondrial DNA depletion syndrome and Charcot-Marie-Tooth (CMT) disease. Although several models including mouse, zebrafish, and cultured human cells, have been developed, the models do not show any neurological defects, which are often observed in patients. Therefore, we knocked down CG11077 (Drosophila Mpv17; dMpv17), an ortholog of human MPV17, in the nervous system in Drosophila melanogaster and investigated the behavioral and cellular phenotypes. The resulting dMpv17 knockdown larvae showed impaired locomotor activity and learning ability consistent with mitochondrial defects suggested by the reductions in mitochondrial DNA and ATP production and the increases in the levels of lactate and reactive oxygen species. Furthermore, an abnormal morphology of the neuromuscular junction, at the presynaptic terminal, was observed in dMpv17 knockdown larvae. These results reproduce well the symptoms of human diseases and partially reproduce the phenotypes of Mpv17-deficient model organisms. Therefore, we suggest that neuron-specific dMpv17 knockdown in Drosophila is a useful model for investigation of MPV17-related hepatocerebral mitochondrial DNA depletion syndrome and CMT caused by Mpv17 dysfunction.

SUBMITTER: Kodani A

PROVIDER: S-EPMC9805426 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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A Drosophila model of the neurological symptoms in Mpv17-related diseases.

Kodani Atsushi A Yamaguchi Mizuki M Itoh Ririka R Huynh Man Anh MA Yoshida Hideki H

Scientific reports 20221231 1

Mutations in the Mpv17 gene are responsible for MPV17-related hepatocerebral mitochondrial DNA depletion syndrome and Charcot-Marie-Tooth (CMT) disease. Although several models including mouse, zebrafish, and cultured human cells, have been developed, the models do not show any neurological defects, which are often observed in patients. Therefore, we knocked down CG11077 (Drosophila Mpv17; dMpv17), an ortholog of human MPV17, in the nervous system in Drosophila melanogaster and investigated the ...[more]

PMID: 36587049

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Project description:BackgroundNonadherence to medication contributes substantially to worse health outcomes. Especially among older adults with chronic illness, multimorbidity leads to complex medication regimes and high nonadherence rates. In previous research, depressive symptomology has been identified as a major contributor to nonadherence, and some authors hypothesize a link via motivational deficits and low self-efficacy. However, the exact mechanisms linking depressive symptomology and nonadherence are not yet understood. This is in part because the often-employed sum scores cannot do justice to the complexity of depressive symptomology; instead, it is recommended to assess the influence of individual symptoms.MethodsFollowing this symptom-based approach, we performed correlation, network and regression analysis using depressive symptoms as depicted by the items of the revised Beck Depression Inventory II (BDI) to assess their influence with nonadherence in N = 731 older adults with chronic neurological diseases. Nonadherence was measured with the self-report Stendal Adherence to Medication Score (SAMS).ResultsEven when controlling for sociodemographic and health-related covariates, the BDI remained the most influential contributor to nonadherence. Across different methods, Loss of Interest and Difficulty with Concentration were identified as particularly influential for nonadherence, linking nonadherence with other affective or somatic BDI items, respectively. Additionally, Fatigue, Problems with Decision Making, Suicidal Thoughts, and Worthlessness contribute to nonadherence.ConclusionUsing a symptom-driven approach, we aimed to understand which depressive symptoms contribute to higher levels of nonadherence. Our results refine previous hypotheses about motivation and control beliefs by suggesting that it is not merely a lack of beliefs in the efficacy of medication that connects depressive symptoms and nonadherence, but rather an overall lack of interest in improving one's health due to feelings of worthlessness and suicidal tendencies. This lack of interest is further substantiated by already sparse resources caused by changes in concentration and fatigue. In order to improve health outcomes and reduce nonadherence, these associations between depressive symptoms must be further understood and targeted in tailored interventions.

Dataset Information

A Drosophila model of the neurological symptoms in Mpv17-related diseases.

Publications

A Drosophila model of the neurological symptoms in Mpv17-related diseases.

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