title: Molecular rescue of DYRK1A overexpression in cystathionine beta synthase-deficient mouse brain by enriched environment combined with voluntary exercise.
abstract: Hyperhomocysteinemia resulting from cystathionine beta synthase (CBS) deficiency can produce cognitive dysfunction. We recently found that CBS-deficient mice exhibit increased expression of the serine/threonine kinase dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A (DYRK1A) in the brain. When dysregulated, DYRK1A contributes to the neurodegeneration, neuronal death, and loss of function observed in neurodegenerative diseases. However, brain plasticity can be improved by interventions like enriched environment combined with voluntary exercise (EE/VE). The present study sought to assess the effects of EE/VE on molecular mechanisms linked to DYRK1A overexpression in the brain of CBS-deficient mice. EE/VE was applied to 3-month-old female CBS-deficient mice for 1 month. Without intervention, CBS-deficient mice exhibited increased DYRK1A and decreased brain-derived neurotrophic factor (BDNF) levels in the cortex and hippocampus. However, EE/VE rescued these altered DYRK1A and BDNF levels in the hippocampus of CBS-deficient mice. We conclude that exercise combined with enriched environment can restore the altered molecular mechanisms in the brain of CBS-deficient mice.
authors.affiliation: Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative (BFA), Université Paris Diderot, UMR 8251 CNRS, 75205, Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Souchet
authors.forename: Alizée
authors.initials: A
authors.lastname: Latour
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Gu
authors.forename: Fabrice
authors.initials: F
authors.lastname: Daubigney
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Paul
authors.forename: Jean-Maurice
authors.initials: JM
authors.lastname: Delabar
authors.forename: Nathalie
authors.initials: N
authors.lastname: Janel
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000172:deficiency* / Q000235:genetics; D005260:Female; D051379:Mice; D005082:Physical Exertion; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D000097603:Dyrk Kinases
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D003541:Cystathionine beta-Synthase; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D000097603:Dyrk Kinases