Modeling of Myotonic Dystrophy Cardiac Phenotypes in Drosophila

Abstract

After respiratory distress, cardiac dysfunction is the second most common cause of fatality associated with the myotonic dystrophy (DM) disease. Despite the prevalance of heart failure in DM, physiopathological studies on heart symptoms have been relatively scarce because few murine models faithfully reproduce the cardiac disease. Consequently, only a small number of candidate compounds have been evaluated in this specific phenotype. To help cover this gap Drosophila combines the amenability of its invertebrate genetics with the possibility of quickly acquiring physiological parameters suitable for meaningful comparisons with vertebrate animal models and humans. Here we review available descriptions of cardiac disease in DM type 1 and type 2, and three recent papers reporting the cardiac toxicity of non-coding CUG (DM1) and CCUG (DM2) repeat RNA in flies. Notably, flies expressing CUG or CCUG RNA in their hearts developed strong arrhythmias and had reduced fractional shortening, which correlates with similar phenotypes in DM patients. Overexpression of Muscleblind, which is abnormally sequestered by CUG and CCUG repeat RNA, managed to strongly suppress arrhythmias and fractional shortening, thus demonstrating that Muscleblind depletion causes cardiac phenotypes in flies. Importantly, small molecules pentamidine and daunorubicin were able to rescue cardiac phenotypes by releasing Muscleblind from sequestration. Taken together, fly heart models have the potential to make important contributions to the understanding of the molecular causes of cardiac dysfunction in DM and in the quick assessment of candidate therapeutics.

Alexithymia Is Associated with Reduced Quality of Life and Increased Caregiver Burden in Parkinson’s Disease

“…Quality of life in PD is reduced in all disease stages. Contributing factors are motor and non-motor symptoms [ 6 , 9 , 28 , 38 , 39 , 40 ]. In the last decade, the influence of non-motor symptoms was extensively studied [ 41 ].…”

“…Because the PDQ-8 is only constructed and validated for PD patients, the HR-QoL of the caregiver could not be assessed by the PDQ-8. As done in other studies, caregivers of PwP with possible cognitive impairment were asked to assist patients in completing the study questionnaires to ensure correct results and avoid anosognosia [ 6 , 28 , 33 ]. Disease specific burden of the caregivers was assessed by the newly developed and validated German version of the Parkinson’s disease caregiver burden questionnaire (PDCB) [ 28 , 33 , 34 ].…”

“…These symptoms result from degeneration of the nigro-striatal dopaminergic projection [ 4 , 5 ]. However, PwP also suffer from neuropsychiatric symptoms like depression, anxiety, apathy, and impulse-control disorders [ 6 , 7 , 8 , 9 ]. Some neuropsychiatric symptoms may arise during the degeneration of the meso-limbic dopaminergic projection and secondary maladaptive changes [ 10 , 11 , 12 , 13 , 14 ].…”

One-Stop Method to Measure Multiple Cardiac Performance Endpoints in Daphnia and Zebrafish by Kymograph

“…This method has been used to measure heartbeat in insect [29], crab [30] and freshwater mussel [31]. In Drosophila, Chakraborty et al [32] used kymograph method for visualization of heart movement within a period, allowing them to obtain heart-related data such as EDD, ESD, HP, SI, and DI. The current kymograph-based method can be considered as a semi-automated tool for multiple heart parameter measurement by combining several tools like image stabilizer, BAR plugin and several macros to facilitate its overall performance.…”

Measurement of Multiple Cardiac Performance Endpoints in Daphnia and Zebrafish by Kymograph

“…This method has also been used to measure heartbeat in insects [43], crabs [44], and freshwater mussel [45]. In Drosophila, Chakraborty et al [46] used the kymograph method for visualization of heart movement within a period, allowing them to obtain heart-related data such as EDD, ESD, HP, SI, and DI. The current kymograph-based method can be considered a semi-automated tool for multiple heart parameter measurement by combining several tools like image stabilizer, BAR plugin, and several macros to facilitate its overall performance.…”