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Adult rat myelin enhances axonal outgrowth from neural stem cells.

2018

Axon regeneration after spinal cord injury (SCI) is attenuated by growth inhibitory molecules associated with myelin. We report that rat myelin stimulated the growth of axons emerging from rat neural progenitor cells (NPCs) transplanted into sites of SCI in adult rat recipients. When plated on a myelin substrate, neurite outgrowth from rat NPCs and from human induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) was enhanced threefold. In vivo, rat NPCs and human iPSC-derived NSCs extended greater numbers of axons through adult central nervous system white matter than through gray matter and preferentially associated with rat host myelin. Mechanistic investigations excluded …

“Pro-youthful” factors in the “labyrinth” of cardiac rejuvenation

2016

IF 3.350; International audience; The mechanisms of aging and senescence include various endogenous and exogenous factors. Among cardiovascular diseases, heart failure is a typical age-related disease. New strategies to restore cardiomyocyte cells have been reported: endogenous substances that can regenerate the heart's cardiomyocytes have been described: follistatin like 1 (FSTL1), growth-differentiation factor 11 (GDF11) and insulin-like growth factor 1 (IGF-I). Manipulation of the different anti and pro-pathways is essential to discover new approaches to regenerative therapies. (C) 2016 Elsevier Inc. All rights reserved.

Intensified mitophagy in skeletal muscle with aging is downregulated by PGC-1alpha overexpression in vivo.

2018

Mitochondrial dysfunction plays an important role in the etiology of age-related muscle atrophy known as sarcopenia. PGC-1α is positioned at the center of crosstalk in regulating mitochondrial quality control, but its role in mitophagy in aged skeletal muscle is currently unclear. The present study investigated the effects of aging and PGC-1α overexpression via in vivo DNA transfection on key mitophagy protein markers, as well as mitochondrial dynamics related proteins, metabolic function and antioxidant capacity in mouse muscle. C57BL/6J mice at the age of 2 mo (young, Y; N = 14) and 24 mo (old, O; N = 14) were transfected in vivo with either PGC-1α DNA (OE, N = 7) or GFP (N = 7) into the …

Characterization of NO-Induced Nitrosative Status in Human Placenta from Pregnant Women with Gestational Diabetes Mellitus

2017

Dysregulation of NO production is implicated in pregnancy-related diseases, including gestational diabetes mellitus (GDM). The role of NO and its placental targets in GDM pregnancies has yet to be determined. S-Nitrosylation is the NO-derived posttranslational protein modification that can modulate biological functions by forming NO-derived complexes with longer half-life, termed S-nitrosothiol (SNO). Our aim was to examine the presence of endogenous S-nitrosylated proteins in cysteine residues in relation to antioxidant defense, apoptosis, and cellular signal transduction in placental tissue from control (n=8) and GDM (n=8) pregnancies. S-Nitrosylation was measured using the biotin-switch …

2019

Traumatic brain injury (TBI) is a frequent pathology and associated with poor outcome in the aged population. We recently observed accelerated cerebral inflammation in aged mice in response to TBI. Candesartan is a potent specific inhibitor of angiotensin II receptor type 1 (AT1) which limits cerebral inflammation and brain damage in juvenile animals after experimental TBI. In the present study, we show significantly lower posttraumatic AT1 mRNA levels in aged (21 months) compared to young (2 months) mice. Despite low cerebral At1 expression, pharmacologic blockade by treatment with candesartan (daily, beginning 30 minutes after experimental TBI by controlled cortical impact [CCI]) was high…

Biological and biophysics aspects of metformin-induced effects: cortex mitochondrial dysfunction and promotion of toxic amyloid pre-fibrillar aggrega…

2016

The onset of Alzheimer disease (AD) is influenced by several risk factors comprising diabetes. Within this context, antidiabetic drugs, including metformin, are investigated for their effect on AD. We report that in the C57B6/J mice, metformin is delivered to the brain where activates AMP-activated kinase (AMPK), its molecular target. This drug affects the levels of β- secretase (BACE1) and β-amyloid precursor protein (APP), promoting processing and aggregation of β-amyloid (Aβ), mainly in the cortex region. Moreover, metformin induces mitochondrial dysfunction and cell death by affecting the level and conformation of Translocase of the Outer Membrane 40 (TOM40), voltage-dependent anion-sel…

Longevity-related molecular pathways are subject to midlife “switch” in humans

2019

Emerging evidence indicates that molecular aging may follow nonlinear or discontinuous trajectories. Whether this occurs in human neuromuscular tissue, particularly for the noncoding transcriptome, and independent of metabolic and aerobic capacities, is unknown. Applying our novel RNA method to quantify tissue coding and long noncoding RNA (lncRNA), we identified ~800 transcripts tracking with age up to ~60 years in human muscle and brain. In silico analysis demonstrated that this temporary linear “signature” was regulated by drugs, which reduce mortality or extend life span in model organisms, including 24 inhibitors of the IGF‐1/PI3K/mTOR pathway that mimicked, and 5 activators that oppos…

Heat shock protein (Hsp) regulation by muscarinic acetylcholine receptor (mAChR) activation in the rat hippocampus.

2018

The cholinergic system plays a crucial role in modulating in the central nervous system physiological responses such as neurogenesis, neuronal differentiation, synaptic plasticity, and neuroprotection. In a recent study, we showed that Oxotremorine-M, a non-selective muscarinic acetylcholine receptor agonist, is able to transactivate the fibroblast growth factor receptor and to produce a significant increase in the hippocampal primary neurite outgrowth. In the present study we aimed to explore in the rat hippocampus the possible effect of acute or chronic treatment with Oxotremorine-M on some heat shock proteins (Hsp60, Hsp70, Hsp90) and on activation of related transcription factor heat sh…

Glucagon-like peptide-1 (GLP-1) receptor agonists and their cardiovascular benefits-The role of the GLP-1 receptor.

2021

Cardiovascular outcome trials revealed cardiovascular benefits for type 2 diabetes mellitus patients when treated with long-acting glucagon-like peptide-1 (GLP-1) receptor agonists. In the last decade, major advances were made characterising the physiological effects of GLP-1 and its action on numerous targets including brain, liver, kidney, heart and blood vessels. However, the effects of GLP-1 and receptor agonists, and the GLP-1 receptor on the cardiovascular system have not been fully elucidated. We compare results from cardiovascular outcome trials of GLP-1 receptor agonists and review pleiotropic clinical and preclinical data concerning cardiovascular protection beyond glycaemic contr…

Transferability of PCR-based diagnostic protocols: An international collaborative case study assessing protocols targeting the quarantine pine pathog…

2019

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