Long-term dietary administration of valproic acid does not affect, while retinoic acid decreases, the lifespan of G93A mice, a model for amyotrophic lateral sclerosis

Mice bearing the mutated gene for Cu/Zn superoxide dismutase (G93A) are a good model for human amyotrophic lateral sclerosis (ALS). They develop progressive limb paralysis paralleled by loss of motor neurons of the cervical and lumbar spinal cord, which starts at 3–3.5 months of age and ends with de...

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Published in:	Muscle & nerve Vol. 39; no. 4; pp. 548 - 552
Main Authors:	Crochemore, Cristophe, Virgili, Marco, Bonamassa, Barbara, Canistro, Donatella, Pena-Altamira, Emiliano, Paolini, Moreno, Contestabile, Antonio
Format:	Journal Article
Language:	English
Published:	Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-04-2009 Wiley
Subjects:	Acetylcholinesterase - metabolism Amyotrophic Lateral Sclerosis - drug therapy Amyotrophic Lateral Sclerosis - genetics Amyotrophic Lateral Sclerosis - mortality Animal Feed Animals Antineoplastic Agents - pharmacology Biological and medical sciences Choline O-Acetyltransferase - metabolism Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Disease Models, Animal Female GABA Agents - pharmacology Gene Dosage Humans Life Expectancy Male Medical sciences Mice Mice, Transgenic Nerve Degeneration - drug therapy Nerve Degeneration - mortality Neurology Superoxide Dismutase - genetics Superoxide Dismutase-1 Tretinoin - pharmacology Valproic Acid - pharmacology Animal model Cholinergic neuron Spinal cord G93A mice Motor system disorder Central nervous system Superoxide dismutase Motor neuron Signal transduction Degenerative disease Paralysis Neurological disorder Human Nervous system diseases Enzyme Deficiency Rodentia Amyotrophic lateral sclerosis Long term Cervical spinal cord cholinergic neurons Vertebrata Mammalia Treatment Mouse Cell death motor neuron degeneration Central nervous system disease Oxidoreductases Spinal cord disease
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Summary:	Mice bearing the mutated gene for Cu/Zn superoxide dismutase (G93A) are a good model for human amyotrophic lateral sclerosis (ALS). They develop progressive limb paralysis paralleled by loss of motor neurons of the cervical and lumbar spinal cord, which starts at 3–3.5 months of age and ends with death at 4–5 months. Several treatments have been attempted to delay clinical symptoms and to extend lifespan, and some have had modest beneficial effects. One such treatment, based on long‐term administration of valproic acid (VPA), resulted in controversial results. We report here that, while dietary supplementation with high VPA dosage slows down motor neuron death, as assessed by measurement of a specific marker for cholinergic neurons in the spinal cord, it has no significant effect on lifespan. Recently, the hypothesis has been put forward that a deficiency of retinoic acid (RA) and its signaling may have a role in ALS. We report that long‐term dietary supplementation with RA has no effect on the decrease of the cholinergic marker in the spinal cord, but it significantly shortens lifespan of G93A mice. Muscle Nerve 39: 548–552, 2009
Bibliography:	ArticleID:MUS21260 istex:4FCDC5DBF005EB50665AD264954F9265621050AD Italian Ministry for Universities and Research (FIRB scheme) ark:/67375/WNG-03VZC79X-4 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0148-639X 1097-4598
DOI:	10.1002/mus.21260