Developmental vitamin D deficiency alters brain protein expression in the adult rat: implications for neuropsychiatric disorders.
An increased risk for multiple sclerosis and schizophrenia is observed at increasing latitude and in patients born in winter or spring. To explore a possible link between maternal vitamin D deficiency and these brain disorders, we examined the impact of prenatal hypovitaminosis D on protein expression in the adult rat brain. Vitamin D-deficient female rats were mated with vitamin D normal males. Pregnant females were kept vitamin D-deficient until birth whereupon they were returned to a control diet. At week 10, protein expression in the progeny's prefrontal cortex and hippocampus was compared with control animals using silver staining 2-D gels associated with MS and newly devised data mining software. Developmental vitamin D (DVD) deficiency caused a dysregulation of 36 brain proteins involved in several biological pathways including oxidative phosphorylation, redox balance, cytoskeleton maintenance, calcium homeostasis, chaperoning, PTMs, synaptic plasticity and neurotransmission. A computational analysis of these data revealed that (i) nearly half of the molecules dysregulated in our animal model have also been shown to be misexpressed in either schizophrenia and/or multiple sclerosis and (ii) an impaired synaptic network may be a consequence of mitochondrial dysfunction.
Almeras
Lionel
L
Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, CNRS UMR 6184, Faculté de Médecine, Université de la Méditerranée, Marseille, France.
Eyles
Darryl
D
Benech
Philippe
P
Laffite
Daniel
D
Villard
Claude
C
Patatian
Angela
A
Boucraut
Jose
J
Mackay-Sim
Alan
A
McGrath
John
J
Féron
François
F
D000818:Animals; D001921:Brain / Q000378:metabolism*; D005260:Female; D001523:Mental Disorders / Q000378:metabolism*; D009422:Nervous System Diseases / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology*; D011506:Proteins / Q000235:genetics*; D051381:Rats; D014808:Vitamin D Deficiency / Q000378:metabolism*
D011506:Proteins