title: Reductions in kinesin expression are associated with nitric oxide-induced axonal damage.
abstract: Axonal injury is often characterized by axonal transport defects and abnormal accumulation of intra-axonal components. Nitric oxide (NO) has a key role in mediating inflammatory axonopathy in many neurodegenerative diseases, but little is known about how nitrosative/oxidative stress affects axonal transport or whether reductions in kinesin superfamily protein (KIF) expression correlate with axon pathology. KIFs are molecular motors that have a key role in axonal and dendritic transport, and impairment of these mechanisms has been associated with a number of neurological disorders. This study shows that rat cortical neurons exposed to NO display both a time-dependent decrease in KIF gene/protein expression and neurofilament phosphorylation in addition to a reduction in axonal length and neuronal survival. Because mesenchymal stem cells (MSCs) represent a promising therapeutic candidate for neuronal/axonal repair, this study analyzes the capacity of MSCs to protect neurons and axonal transport mechanisms from NO damage. Results show that coculture of MSCs with NO-exposed neurons results in the preservation of KIF expression, axonal length, and neuronal survival. Altogether, these results suggest a potential mechanism involved in the disruption of axonal transport and abnormal accumulation of proteins in axons during nitrosative insult. We hypothesize that impaired axonal transport contributes, per se, to progression of injury and provide further evidence of the therapeutic potential of MSCs for neurodegenerative disorders.
authors: Multiple Sclerosis and Stem Cell Group, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom.
authors: Juliana
authors: J
authors: Redondo
authors: Kelly
authors: K
authors: Hares
authors: Alastair
authors: A
authors: Wilkins
authors: Neil
authors: N
authors: Scolding
authors: Kevin
authors: K
authors: Kemp
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001369:Axons / Q000187:drug effects / Q000473:pathology*; D001854:Bone Marrow Cells / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D018920:Coculture Techniques; D004622:Embryo, Mammalian; D016166:Free Radical Scavengers / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D009569:Nitric Oxide / Q000633:toxicity*; D051381:Rats; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D016166:Free Radical Scavengers; D016900:Neurofilament Proteins; C051774:neurofilament protein H; D009569:Nitric Oxide; D016547:Kinesins
keywords: axonal transport; mesenchymal stem cells; motor proteins; neuroprotection; nitrosative stress
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