PN 23.16.01.02

A brief overview of the project

Sarcopenia/cachexia muscle is defined as a loss of muscle mass, decreased muscle strength, and functional striated muscle, leading to disability and reduced quality of life and even the progression of cognitive decline. In Parkinson's disease (PD), for example, 40% of the patients suffering from this syndrome, and 11% of those end up in a severe form. The relationship between the muscle and the neurological examination has not yet been demonstrated. Recent studies have shown that there is an improvement in the symptoms and in some neurodegenerative disorder after physical training is of low intensity, medium to induce favorable changes in the level of striated muscle. In addition, atrophy of the brain related to age, regular physical activity has proven its effectiveness by improving cerebral perfusion, metabolic functions, biogenesis mitochondrial dysfunction and reducing oxidative stress, and neuroinflamația. Experimental models in-vitro and in vivo studies BP, which we have in view, as a "proof of concept", it will allow the extrapolation of the results obtained from the pathology of human PD, possibly in reference to other neurodegenerative diseases affecting the muscles. Skeletal muscle is an endocrine organ that produces and releases miokine (cytokines specific to the muscle), is shown to exert the effects of the endocrine-specific impact on other organs, including the brain. The collaboration with the Hospital, which included they provide access to samples of the blood and CSF of patients with PD. Our study is the the original and features a newat both the national and international levels. This panel of biomarkers of muscle that we want to establish in order to evaluate the communication between the nervous system and the central nervous system, the axis of the muscle, the brain contains both miokine, as well as the markers epigenetici, in particular, the miRNA sites in muscle and the proteins involved in the mechanisms of epigenetic and oxidative stress (DNMTs, SIRTs). 

Project objective:

The establishment of a a panel of biomarkers of muscle circulating edit BP cachexia musclefor the evaluation of the the prognosis of the disease and potential therapeutic targets. This approach will allow the identification of specific molecules that might be able to be reached or completed, in order to delay or prevent the disturbance of cellular mechanisms that underlie the impairment of both tissues on the brain-to-muscle. To this end, we use  the designs of the experimental “proof of concept” in-vitro and in vivo studies. In experimental design in-vitro we use the neuroblaste people in line, SH-SY5Y differentiated into dopaminergic neurons, in which it induces the accumulation of pathological alpha-sinucleină/phospho-alpha-sinucleină by treatment with rotenonă or MPP+. These cells are put in the co-culture with normal cells from the skeletal muscle of human, separated from the line of myoblasts and human HSkMC. They highlight the biomarkers change in quantity/quality to the level of the cell (both cell types) and the growth medium as a result of the interaction by soluble molecules between the two cell populations. Other model in-vitro it is one of the the aging of muscle prematurely induced by antisense oligonucleotides (ASOs) in the cells of murine C2C12 for the development of a splicing alternative in the gene LMNA, which leads to the loss of up to 150 bases from the end of exon 11. The analysis of the biomarkers change in quantity/quality to the level of the cell, and the influence of phenotype on the cells of the cells. To experimental design in vivo studies use of transgenic mice with Parkinson's disease, the human: B6;C3-Tg(Pmp-SNCA* A52T)83Vle/J Follow a significant reduction in weight loss, muscle growth, behavioral changes characteristic for PD, changes in the pathological morphology of the brain, muscle tissue biomarkers of circulating change, before and after the physical exercise of moderate.

The objectives of the project:

1. The establishment of a panel of biomarkers for the co-operation between the tissue by the molecules that are soluble in the model of a “proof of concept” in-vitro by co-cultivation of the dopaminergic neurons of the human, before and after they have been induced by the pathology of pd treatment, with rotenonă, and the cell of the muscle, human positions the sarcopenie induced with the help of the ASOs. 
2. The evaluation of the effect of physical training of moderate impact on the installation, and the progression of damage to the muscle in the animal model of pd by monitoring the parameters of the muscular and neurological. 
3. The establishment of a panel of biomarkers circulating in the model of a “proof-of-concept” in vivo,the for the co-operation between the tissue by soluble molecules as prognostic factors for the progression of the BP to the late stages, and the installation of the damage of the muscle.
4. The establishment of a panel of biomarkers for the prognosis of the circulating in patients with BP, with varying degrees of muscle damage. 

Expected results:

– any changes made to the Parkinson's disease on the degradation of the muscle, through the determination of the panel of biomarkers of muscle, which characterize the more advanced stages of PD.

– the protective effect of physical exercise on BP, as the changes in the brain, as well as the muscle tissue on the brain-to-muscle, striated. 

– the selection panel of biomarkers, circulating change in Parkinson's disease with sarcopenie related: miokine, miRNA, puzzles, markers, epigenetici, and oxidative stress.

Delivery:

Communication social sciences

Bastian A., Manole E. Pathological aspects and classification criteria of inflammatory myopathies, International Pathology Conference of the “Victor Babes” Institute, Bucharest, 2-4 November 2023, Bucharest, Romania, Book of abstracts https://www.ivb.ro/wp-content/uploads/2024/01/REZUMATE-IPC_2023.pdf , Pag 53. Oral presentation

Manole E., Gaina G., Lambresu I., Ceafalan L. The involvement of Parkin in the skeletal muscle phenotype in Parkinson’s disease, International Pathology Conference of the “Victor Babes” Institute, Bucharest, 2-4 November 2023, Bucharest, Romania, Book of abstracts https://www.ivb.ro/wp-content/uploads/2024/01/REZUMATE-IPC_2023.pdf, Pag 55. Oral presentation 

Publications 

Ioghen ° C, Ceafalan CL, Popescu BO. The SH-SY5Y Cell Line In-Vitro Models for Parkinson's Disease Research, in Old Practice for the New Trends. J Integr Neurosci. 2023-Jan 16;22(1):20. doi: 10.31083/j.jin2201020. PMID: 36722247.

Emilia Manole, Laura C. Ceafalan, Gisela F. Gaina, Oana A. Mosoia, Mihai E. Hinescu. Myokine expression in cancer cachexia. In: Cancer research: an interdisciplinary approach. In: Rezaei, N. (eds) Cancer Research: An Interdisciplinary Approach. Interdisciplinary Cancer Research, 2023, vol 1. Springer, Cham. https://doi.org/10.1007/16833_2023_138

Joan Lambrescu, Emilia Manole, Laura, Cristina, Ceafalan, Gerard Hen. The potential benefits of the drug-repositioning in the muscular dystrophies. In: the Potential of Therapeutic strategies for muscular dystrophy. The head. 4. Edited by Gisela Chicken, 2023, IntechOpen. ISBN: 978-1-83768-156-3, Print ISBN: 978-1-83768-155-6