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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
Author(s) -
Crochemore Cristophe,
Virgili Marco,
Bonamassa Barbara,
Canistro Donatella,
PenaAltamira Emiliano,
Paolini Moreno,
Contestabile Antonio
Publication year - 2009
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.21260
Subject(s) - amyotrophic lateral sclerosis , spinal cord , valproic acid , medicine , lumbar spinal cord , cholinergic , neuroprotection , motor neuron , endocrinology , retinoic acid , tretinoin , neuroscience , central nervous system , epilepsy , biology , disease , biochemistry , psychiatry , gene
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