Developmental vitamin D deficiency alters the expression of genes encoding mitochondrial, cytoskeletal and synaptic proteins in the adult rat brain

• DOI: 10.1016/j.jsbmb.2006.12.096
• Publication Date: 2006-12-26T14:08:13Z
• Authors: D. Eyles; L. Almeras; P. Benech; A. Patatian; A. Mackay-Sim; J. McGrath; F. Féron
• Keywords: MESH: Signal Transduction; Male; 0301 basic medicine; Aging; Time Factors; Transcription, Genetic; MESH: Neurons; MESH: Rats, Sprague-Dawley; Rats, Sprague-Dawley; MESH: Aging; MESH: Animals; MESH: Proteins; Cytoskeleton; 730204 Child health; Oligonucleotide Array Sequence Analysis; Neurons; Systems Biology; MESH: Transcription; Brain; Brain development; Synapse; MESH: Gene Expression Regulation; Mitochondria; MESH: Systems Biology; MESH: Vitamin D Deficiency; [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]; Female; Signal Transduction; MESH: Rats; MESH: Mitochondria; 610; MESH: Brain; 03 medical and health sciences; C1; Genetic; 616; MESH: Cytoskeleton; Animals; [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]; Gene array; MESH: Transcription, Genetic; MESH: Time Factors; Hypovitaminosis D; Proteins; Vitamin D Deficiency; MESH: Male; Rats; Gene Expression Regulation; Biochemistry and cell biology; MESH: Oligonucleotide Array Sequence Analysis; Rat; 321204 Mental Health; Sprague-Dawley; Analytical chemistry; MESH: Female

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.