Developmental vitamin D deficiency alters the expression of genes encoding mitochondrial, cytoskeletal and synaptic proteins in the adult rat brain.
Epidemiology has highlighted the links between season of birth, latitude and the prevalence of brain disorders such as multiple sclerosis and schizophrenia. In line with these data, we have hypothesized that "imprinting" with low prenatal vitamin D could contribute to the risk of these two brain disorders. Previously, we have shown that transient developmental hypovitaminosis D induces permanent changes in adult nervous system. The aim of this study was to examine the impact of prenatal hypovitaminosis D on gene expression in the adult rat brain. Vitamin D deficient female rats were mated with undeprived males and the offspring were fed with a control diet after birth. At Week 10, gene expression in the progeny's brain was compared with control animals using Affymetrix gene microarrays. Prenatal hypovitaminosis D causes a dramatic dysregulation of several biological pathways including oxidative phosphorylation, redox balance, cytoskeleton maintenance, calcium homeostasis, chaperoning, post-translational modifications, synaptic plasticity and neurotransmission. A computational analysis of these data suggests that impaired synaptic network may be a consequence of mitochondrial dysfunction. Since disruptions of mitochondrial metabolism have been associated with both multiple sclerosis and schizophrenia, developmental vitamin D deficiency may be a heuristic animal model for the study of these two brain diseases.
Eyles
D
D
Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, QLD 4076, Australia.
Almeras
L
L
Benech
P
P
Patatian
A
A
Mackay-Sim
A
A
McGrath
J
J
Féron
F
F
D000375:Aging / Q000502:physiology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D049490:Systems Biology; D013997:Time Factors; D014158:Transcription, Genetic / Q000235:genetics; D014808:Vitamin D Deficiency / Q000235:genetics / Q000378:metabolism*
D011506:Proteins