Hippocampal mitochondrial dysfunction and psychiatric-relevant behavioral deficits in spinocerebellar ataxia 1 mouse model.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
25 03 2020
Historique:
received: 13 09 2019
accepted: 10 03 2020
entrez: 28 3 2020
pubmed: 28 3 2020
medline: 24 11 2020
Statut: epublish

Résumé

Spinocerebellar ataxia 1 (SCA1) is a devastating neurodegenerative disease associated with cerebellar degeneration and motor deficits. However, many patients also exhibit neuropsychiatric impairments such as depression and apathy; nevertheless, the existence of a causal link between the psychiatric symptoms and SCA1 neuropathology remains controversial. This study aimed to explore behavioral deficits in a knock-in mouse SCA1 (SCA1

Identifiants

pubmed: 32214165
doi: 10.1038/s41598-020-62308-0
pii: 10.1038/s41598-020-62308-0
pmc: PMC7096488
doi:

Substances chimiques

Biomarkers 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5418

Références

Matilla-Dueñas, A., Goold, R. & Giunti, P. Clinical, genetic, molecular, and pathophysiological insights into spinocerebellar ataxia type 1. Cerebellum 7, 106–14 (2008).
pubmed: 18418661 doi: 10.1007/s12311-008-0009-0
Rub, U. et al. Spinocerebellar ataxia type 1 (SCA1): New pathoanatomical and clinico-pathological insights. Neuropathol. Appl. Neurobiol. 38, 665–680 (2012).
pubmed: 22309224 doi: 10.1111/j.1365-2990.2012.01259.x
Paulson, H. L., Shakkottai, V. G., Clark, H. B. & Orr, H. T. Polyglutamine spinocerebellar ataxias-from genes to potential treatments. Nat. Rev. Neurosci. 18, 613–626 (2017).
pubmed: 28855740 pmcid: 6420820 doi: 10.1038/nrn.2017.92
Ma, J., Wu, C., Lei, J. & Zhang, X. Cognitive impairments in patients with spinocerebellar ataxia types 1, 2 and 3 are positively correlated to the clinical severity of ataxia symptoms. Int. J. Clin. Exp. Med. 7, 5765–5771 (2014).
pubmed: 25664104 pmcid: 4307551
McMurtray, A. M., Clark, D. G., Flood, M. K., Perlman, S. & Mendez, M. F. Depressive and memory symptoms as presenting features of spinocerebellar ataxia. J. Neuropsychiatry Clin. Neurosci. 18, 420–2 (2006).
pubmed: 16963595 doi: 10.1176/jnp.2006.18.3.420
Sokolovsky, N., Cook, A., Hunt, H., Giunti, P. & Cipolotti, L. A preliminary characterisation of cognition and social cognition in spinocerebellar ataxia types 2, 1, and 7. Behav. Neurol. 23, 17–29 (2010).
pubmed: 20714058 pmcid: 5434399 doi: 10.1155/2010/395045
Bürk, K. et al. Cognitive deficits in spinocerebellar ataxia type 1, 2, and 3. J. Neurol. 250, 207–11 (2003).
pubmed: 12574952 doi: 10.1007/s00415-003-0976-5
Fancellu, R. et al. Longitudinal study of cognitive and psychiatric functions in spinocerebellar ataxia types 1 and 2. 3134–3143, https://doi.org/10.1007/s00415-013-7138-1 (2013).
pubmed: 24122064 doi: 10.1007/s00415-013-7138-1
Lo, R. Y. et al. Depression and clinical progression in spinocerebellar ataxias. Park. Relat. Disord. 22, 87–92 (2016).
doi: 10.1016/j.parkreldis.2015.11.021
Watase, K. et al. A long CAG repeat in the mouse Sca1 locus replicates SCA1 features and reveals the impact of protein solubility on selective neurodegeneration. Neuron 34, 905–919 (2002).
pubmed: 12086639 pmcid: 12086639 doi: 10.1016/S0896-6273(02)00733-X
Hatanaka, Y., Watase, K., Wada, K. & Nagai, Y. Abnormalities in synaptic dynamics during development in a mouse model of spinocerebellar ataxia type 1. Sci. Rep. 5, 16102 (2015).
pubmed: 26531852 pmcid: 4632040 doi: 10.1038/srep16102
Watase, K. et al. Lithium therapy improves neurological function and hippocampal dendritic arborization in a spinocerebellar ataxia type 1 mouse model. PLoS Med. 4, 0836–0847 (2007).
doi: 10.1371/journal.pmed.0040182
Asher, M., Johnson, A., Zecevic, B., Pease, D. & Cvetanovic, M. ATAXIN-1 REGULATES PROLIFERATION OF HIPPOCAMPAL NEURAL PRECURSORS. Neuroscience 322, 54–65 (2016).
pubmed: 26876606 doi: 10.1016/j.neuroscience.2016.02.011 pmcid: 26876606
Cvetanovic, M., Hu, Y. S. & Opal, P. Mutant Ataxin-1 Inhibits Neural Progenitor Cell Proliferation in SCA1. Cerebellum 16, 340–347 (2017).
pubmed: 27306906 pmcid: 27306906 doi: 10.1007/s12311-016-0794-9
Khacho, M., Harris, R. & Slack, R. S. Mitochondria as central regulators of neural stem cell fate and cognitive function. Nat. Rev. Neurosci., https://doi.org/10.1038/s41583-018-0091-3 (2018).
doi: 10.1038/s41583-018-0091-3
Khacho, M. et al. Mitochondrial dysfunction underlies cognitive defects as a result of neural stem cell depletion and impaired neurogenesis. 26, 3327–3341 (2017).
Devine, M. J. & Kittler, J. T. Mitochondria at the neuronal presynapse in health and disease. Nat. Rev. Neurosci. 19, 63–80 (2018).
pubmed: 29348666 doi: 10.1038/nrn.2017.170
Mattson, M. P., Gleichmann, M. & Cheng, A. Review Mitochondria in Neuroplasticity and Neurological Disorders. Neuron 60, 748–766 (2008).
pubmed: 19081372 pmcid: 2692277 doi: 10.1016/j.neuron.2008.10.010
Gan, L., Cookson, M. R., Petrucelli, L. & La Spada, A. R. Converging pathways in neurodegeneration, from genetics to mechanisms. Nat. Neurosci. 21, 1300–1309 (2018).
pubmed: 30258237 pmcid: 6278826 doi: 10.1038/s41593-018-0237-7
Allen, J., Romay-Tallon, R., Brymer, K. J., Caruncho, H. J. & Kalynchuk, L. E. Mitochondria and mood: Mitochondrial dysfunction as a key player in the manifestation of depression. Front. Neurosci. 12, 1–13 (2018).
doi: 10.3389/fnins.2018.00386
Marazziti, D. et al. Psychiatric disorders and mitochondrial dysfunctions. Eur. Rev. Med. Pharmacol. Sci. 16, 270–275 (2012).
pubmed: 22428481 pmcid: 22428481
Pereira, C. et al. Mitochondrial agents for bipolar disorder. Int. J. Neuropsychopharmacol. 21, 550–569 (2018).
pubmed: 29596661 pmcid: 6007750 doi: 10.1093/ijnp/pyy018
Ferro, A. et al. Short-term succinic acid treatment mitigates cerebellar mitochondrial OXPHOS dysfunction, neurodegeneration and ataxia in a Purkinje-specific spinocerebellar ataxia type 1 (SCA1) mouse model. PLoS One 12, 1–20 (2017).
doi: 10.1371/journal.pone.0188425
Stucki, D. M. et al. Free Radical Biology and Medicine Mitochondrial impairments contribute to Spinocerebellar ataxia type 1 progression and can be ameliorated by the mitochondria-targeted antioxidant MitoQ. Free Radic. Biol. Med. 97, 427–440 (2016).
pubmed: 27394174 doi: 10.1016/j.freeradbiomed.2016.07.005 pmcid: 27394174
Ripolone, M. et al. Purkinje cell cox deficiency and mtdna depletion in an animal model of spinocerebellar ataxia type 1. J. Neurosci. Res. 96, 1576–1585 (2018).
pubmed: 30113722 doi: 10.1002/jnr.24263 pmcid: 30113722
Sánchez, I., Balagué, E. & Matilla-Dueñas, A. Ataxin-1 regulates the cerebellar bioenergetics proteome through the GSK3β-mTOR pathway which is altered in Spinocerebellar ataxia type 1 (SCA1). Hum. Mol. Genet. 25, 4021–4040 (2016).
pubmed: 27466200 pmcid: 27466200 doi: 10.1093/hmg/ddw242
Varbanov, H. & Dityatev, A. Regulation of extrasynaptic signaling by polysialylated NCAM: Impact for synaptic plasticity and cognitive functions. Mol. Cell. Neurosci. 81, 12–21 (2017).
pubmed: 27865768 doi: 10.1016/j.mcn.2016.11.005 pmcid: 27865768
Dityatev, A. et al. Polysialylated neural cell adhesion molecule promotes remodeling and formation of hippocampal synapses. J. Neurosci. 24, 9372–9382 (2004).
pubmed: 15496673 pmcid: 6730092 doi: 10.1523/JNEUROSCI.1702-04.2004
Kang, K. et al. Tissue-based metabolic labeling of polysialic acids in living primary hippocampal neurons. Proc. Natl. Acad. Sci. USA 112, E241–E248 (2015).
pubmed: 25564666 doi: 10.1073/pnas.1419683112 pmcid: 25564666
Boldrini, M. et al. Human Hippocampal Neurogenesis Persists throughout Aging. Cell Stem Cell 589–599, https://doi.org/10.1016/j.stem.2018.03.015 (2018).
pubmed: 29625071 pmcid: 5957089 doi: 10.1016/j.stem.2018.03.015
Doerrier, C. et al. High-Resolution FluoRespirometry and OXPHOS Protocols for Human Cells, Permeabilized Fibers from Small Biopsies of Muscle, and Isolated Mitochondria. in 31–70, https://doi.org/10.1007/978-1-4939-7831-1_3 (Humana Press, New York, NY, 2018).
doi: 10.1007/978-1-4939-7831-1_3
Cvetanovic, M., Patel, J. M., Marti, H. H., Kini, A. R. & Opal, P. Vascular endothelial growth factor ameliorates the ataxic phenotype in a mouse model of spinocerebellar ataxia type 1. Nat. Med. 17, 1445–7 (2011).
pubmed: 22001907 pmcid: 22001907 doi: 10.1038/nm.2494
Cvetanovic, M., Ingram, M., Orr, H. & Opal, P. Early activation of microglia and astrocytes in mouse models of Spinocerebellar Ataxia Type 1. Neuroscience 48, 289–299 (2015).
doi: 10.1016/j.neuroscience.2015.01.003
Andersen, P., Morris, R., Amaral, D., Bliss, T. & Keefe, J. O. The Hippocampus Book, https://doi.org/10.1093/acprof:oso/9780195100273.001.0001 (Oxford University Press, 2006).
Yousef, A. et al. Neuron loss and degeneration in the progression of TDP-43 in frontotemporal lobar degeneration. Acta Neuropathol. Commun. 5, 68 (2017).
pubmed: 28877758 pmcid: 5586052 doi: 10.1186/s40478-017-0471-3
Duan, W. et al. Novel Insights into NeuN: from Neuronal Marker to Splicing Regulator. Mol. Neurobiol. 53, 1637–1647 (2016).
pubmed: 25680637 doi: 10.1007/s12035-015-9122-5
Wu, K. L. et al. Loss of neuronal protein expression in mouse hippocampus after irradiation. J. Neuropathol. Exp. Neurol. 69, 272–280 (2010).
pubmed: 20142763 doi: 10.1097/NEN.0b013e3181d1afe4
Collombet, J. M. et al. Early reduction of NeuN antigenicity induced by soman poisoning in mice can be used to predict delayed neuronal degeneration in the hippocampus. Neurosci. Lett. 398, 337–342 (2006).
pubmed: 16472911 doi: 10.1016/j.neulet.2006.01.029
Suh, J. et al. Loss of Ataxin-1 Potentiates Alzheimer’s Pathogenesis by Elevating Cerebral BACE1 Transcription. Cell 178, 1159–1175.e17 (2019).
pubmed: 31442405 doi: 10.1016/j.cell.2019.07.043
Mellesmoen, A., Sheeler, C., Ferro, A., Rainwater, O. & Cvetanovic, M. Brain derived neurotrophic factor (BDNF) delays onset of pathogenesis in transgenic mouse model of spinocerebellar ataxia type 1 (SCA1). Front. Cell. Neurosci. 12, 1–8 (2019).
doi: 10.3389/fncel.2018.00509
Liu, P. Z. & Nusslock, R. Exercise-mediated neurogenesis in the hippocampus via BDNF. Front. Neurosci. 12, 1–6 (2018).
Ghosh, A., Carnahan, J. & Greenberg, M. E. Requirement for BDNF in activity-dependent survival of cortical neurons. Science (80-.). 263, 1618–1623 (1994).
doi: 10.1126/science.7907431
Lipsky, R. H. & Marini, A. M. Brain-derived neurotrophic factor in neuronal survival and behavior-related plasticity. Ann. N. Y. Acad. Sci. 1122, 130–143 (2007).
pubmed: 18077569 doi: 10.1196/annals.1403.009
Schoenfeld, T. J., McCausland, H. C., Morris, H. D., Padmanaban, V. & Cameron, H. A. Stress and Loss of Adult Neurogenesis Differentially Reduce Hippocampal Volume. Biol. Psychiatry 82, 914–923 (2017).
pubmed: 28629541 pmcid: 5683934 doi: 10.1016/j.biopsych.2017.05.013
Bessa, J. M. et al. The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling. Mol. Psychiatry 14, 764–773 (2009).
pubmed: 18982002 doi: 10.1038/mp.2008.119
Travis, S. et al. Dentate gyrus volume and memory performance in major depressive disorder. J. Affect. Disord. 172, 159–164 (2015).
pubmed: 25451411 doi: 10.1016/j.jad.2014.09.048
Huang, Y. et al. Structural changes in hippocampal subfields in major depressive disorder: A high-field magnetic resonance imaging study. Biol. Psychiatry 74, 62–68 (2013).
pubmed: 23419546 doi: 10.1016/j.biopsych.2013.01.005
Cao, B. et al. Hippocampal subfield volumes in mood disorders. Mol. Psychiatry 22, 1352–1358 (2017).
pubmed: 28115740 pmcid: 5524625 doi: 10.1038/mp.2016.262
Anacker, C. & Hen, R. Adult hippocampal neurogenesis and cognitive flexibility — linking memory and mood. Nat. Rev. Neurosci., https://doi.org/10.1038/nrn.2017.45 (2017).
pubmed: 28469276 pmcid: 6261347 doi: 10.1038/nrn.2017.45
Watanabe, Y., Gould, E. & McEwen, B. S. Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain Res. 588, 341–345 (1992).
pubmed: 1393587 doi: 10.1016/0006-8993(92)91597-8 pmcid: 1393587
Tuma, J., Kolinko, Y., Vozeh, F. & Cendelin, J. Mutation-related differences in exploratory, spatial, and depressive-like behavior in pcd and Lurcher cerebellar mutant mice. Front. Behav. Neurosci. 9, 116 (2015).
pubmed: 26029065 pmcid: 4429248 doi: 10.3389/fnbeh.2015.00116
Monnier, C. & Lalonde, R. Elevated +-maze and hole-board exploration in lurcher mutant mice. Brain Res. 702, 169–172 (1995).
pubmed: 8846072 doi: 10.1016/0006-8993(95)01036-5 pmcid: 8846072
Hilber, P., Lorivel, T., Delarue, C. & Caston, J. Stress and anxious-related behaviors in Lurcher mutant mice. Brain Res. 1003, 108–112 (2004).
pubmed: 15019569 doi: 10.1016/j.brainres.2004.01.008 pmcid: 15019569
Cendelin, J., Tuma, J., Korelusova, I. & Vozeh, F. The effect of genetic background on behavioral manifestation of Grid2Lc mutation. Behav. Brain Res. 271, 218–227 (2014).
pubmed: 24937052 doi: 10.1016/j.bbr.2014.06.023 pmcid: 24937052
Cendelin, J. & Tichanek, F. Cerebellar degeneration averts blindness-induced despaired behavior during spatial task in mice. Neurosci. Lett. 134854, https://doi.org/10.1016/j.neulet.2020.134854 (2020).
pubmed: 32088197 doi: 10.1016/j.neulet.2020.134854 pmcid: 32088197
Yamamoto, M., Kim, M., Imai, H., Itakura, Y. & Ohtsuki, G. Microglia-Triggered Plasticity of Intrinsic Excitability Modulates Psychomotor Behaviors in Acute Cerebellar Inflammation. Cell Rep. 28, 2923–2938.e8 (2019).
pubmed: 31509752 doi: 10.1016/j.celrep.2019.07.078 pmcid: 31509752
Krook-Magnuson, E., Szabo, G. G., Armstrong, C., Oijala, M. & Soltesz, I. Cerebellar Directed Optogenetic Intervention Inhibits Spontaneous Hippocampal Seizures in a Mouse Model of Temporal Lobe Epilepsy. eNeuro 1, 1–27 (2014).
doi: 10.1523/ENEURO.0005-14.2014
Yu, W. & Krook-Magnuson, E. Cognitive Collaborations: Bidirectional Functional Connectivity Between the Cerebellum and the Hippocampus. Front. Syst. Neurosci. 9, 1–10 (2015).
doi: 10.3389/fnsys.2015.00177
Lefort, J. M. et al. Impaired cerebellar Purkinje cell potentiation generates unstable spatial map orientation and inaccurate navigation. Nat. Commun. 10, 2251 (2019).
pubmed: 31113954 pmcid: 6529420 doi: 10.1038/s41467-019-09958-5
Fernandez, A. et al. Mitochondrial Dysfunction Leads to Cortical Under-Connectivity and Cognitive Impairment. Neuron 1–16, https://doi.org/10.1016/j.neuron.2019.04.013 (2019).
pubmed: 31079872 doi: 10.1016/j.neuron.2019.04.013 pmcid: 31079872
Arrázola, M. S. et al. Mitochondria in Developmental and Adult Neurogenesis. Neurotox. Res. 257–267, https://doi.org/10.1007/s12640-018-9942-y (2018).
pubmed: 30215161 doi: 10.1007/s12640-018-9942-y pmcid: 30215161
Oettinghaus, B. et al. Synaptic dysfunction, memory deficits and hippocampal atrophy due to ablation of mitochondrial fission in adult forebrain neurons. Cell Death Differ. 23, 18–28 (2016).
pubmed: 25909888 doi: 10.1038/cdd.2015.39 pmcid: 25909888
Bachmann, R. F. et al. Common effects of lithium and valproate on mitochondrial functions: Protection against methamphetamine-induced mitochondrial damage. Int. J. Neuropsychopharmacol. 12, 805–822 (2009).
pubmed: 19149911 pmcid: 2779114 doi: 10.1017/S1461145708009802
Peng, M. et al. Inhibiting cytosolic translation and autophagy improves health in mitochondrial disease. Hum. Mol. Genet. 24, 4829–4847 (2015).
pubmed: 26041819 pmcid: 4527487 doi: 10.1093/hmg/ddv207
Tam, Z. Y., Gruber, J., Ng, L. F., Halliwell, B. & Gunawan, R. Effects of lithium on age-related decline in mitochondrial turnover and function in caenorhabditis elegans. Journals Gerontol. - Ser. A Biol. Sci. Med. Sci. 69, 810–820 (2014).
doi: 10.1093/gerona/glt210
Maurer, I. C., Schippel, P. & Volz, H. P. Lithium-induced enhancement of mitochondrial oxidative phosphorylation in human brain tissue. Bipolar Disord. 11, 515–522 (2009).
pubmed: 19624390 doi: 10.1111/j.1399-5618.2009.00729.x pmcid: 19624390
Bernardo, T. C. et al. Physical Exercise and Brain Mitochondrial Fitness: The Possible Role Against Alzheimer’s Disease. Brain Pathol. 26, 648–663 (2016).
pubmed: 27328058 doi: 10.1111/bpa.12403 pmcid: 27328058
Sarkar, A. et al. Efficient Generation of CA3 Neurons from Human Pluripotent Stem Cells Enables Modeling of Hippocampal Connectivity In Vitro. Cell Stem Cell 22, 684–697.e9 (2018).
pubmed: 29727680 pmcid: 6345574 doi: 10.1016/j.stem.2018.04.009
Hiragi, T. et al. Differentiation of human induced pluripotent stem cell (hiPSC)-derived neurons in mouse hippocampal slice cultures. Front. Cell. Neurosci. 11, 1–10 (2017).
doi: 10.3389/fncel.2017.00143
Cendelin, J. et al. Long-Term Development of Embryonic Cerebellar Grafts in Two Strains of Lurcher Mice. Cerebellum 17, 1–10 (2018).
doi: 10.1007/s12311-018-0928-3
Purkartova, Z., Tichanek, F., Kolinko, Y. & Cendelin, J. Embryonic Cerebellar Graft Morphology Differs in Two Mouse Models of Cerebellar Degeneration. The Cerebellum 18, 855–865 (2019).
pubmed: 31418135 doi: 10.1007/s12311-019-01067-9
Salomova, M., Tichanek, F., Jelinkova, D. & Cendelin, J. Abnormalities in the cerebellar levels of trophic factors BDNF and GDNF in pcd and Lurcher cerebellar mutant mice. Neurosci. Lett. 134870, https://doi.org/10.1016/j.neulet.2020.134870 (2020).
pubmed: 32109557 doi: 10.1016/j.neulet.2020.134870
Komlódi, T. et al. Comparison of Mitochondrial Incubation Media for Measurement of Respiration and Hydrogen Peroxide Production. in 137–155, https://doi.org/10.1007/978-1-4939-7831-1_8 (Humana Press, New York, NY, 2018).
doi: 10.1007/978-1-4939-7831-1_8
R Development Core Team. R: A Language and Environment for Statistical Computing. (2016).
Diciccio, T. J. & Efron, B. Bootstrap Confidence Intervals. Stat. Sci. 11, 189–212 (1996).
doi: 10.1214/ss/1032280214
Torchiano, M. Effsize - a package for efficient effect size computation., https://doi.org/10.5281/ZENODO.1480624 (2016).
Canty, A. & Ripley, B. D. boot: Bootstrap R (S-Plus) Functions. (2017).
Pinheiro, J., Bates, D., DebRoy, S., Sarkar, D. & R Core Team. nlme: Linear and Nonlinear Mixed Effects Models (2018).
Luo, D., Ganesh, S. & Koolaard, J. predictmeans: Calculate Predicted Means for Linear Models (2018).
Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B 57, 289–300 (1995).
Oksanen, J. et al. Package ‘vegan’ Title Community Ecology Package (2019).
Robin, X. et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics 12, 77 (2011).
pubmed: 21414208 pmcid: 3068975 doi: 10.1186/1471-2105-12-77
Wood, S. N. Fast stable restricted maximum likelihood and marginal likelihood estimation of semiparametric generalized linear models. J. R. Stat. Soc. Ser. B (Statistical Methodol. 73, 3–36 (2011).
doi: 10.1111/j.1467-9868.2010.00749.x

Auteurs

Filip Tichanek (F)

Department of Pathological Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia. f.tichanek@gmail.com.
Laboratory of Neurodegenerative Disorders, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia. f.tichanek@gmail.com.

Martina Salomova (M)

Department of Pathological Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.
Laboratory of Neurodegenerative Disorders, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.

Jan Jedlicka (J)

Department of Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.
Mitochondrial Laboratory, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.

Jitka Kuncova (J)

Department of Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.
Mitochondrial Laboratory, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.

Pavel Pitule (P)

Laboratory of Tumor Biology, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.

Tereza Macanova (T)

Department of Biology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.

Zuzana Petrankova (Z)

Department of Pathological Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.

Zdenek Tuma (Z)

Laboratory of Proteomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.

Jan Cendelin (J)

Department of Pathological Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.
Laboratory of Neurodegenerative Disorders, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.

Articles similaires

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male
Humans Meals Time Factors Female Adult

Classifications MeSH