The transcriptomic response of mixed neuron-glial cell cultures to 1,25-dihydroxyvitamin d3 includes genes limiting the progression of neurodegenerative diseases.

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The transcriptomic response of mixed neuron-glial cell

cultures to 1,25-dihydroxyvitamin d3 includes genes

limiting the progression of neurodegenerative diseases.

Marie-France Nissou, Jacques Brocard, Michèle El Atifi, Audrey Guttin,

Annie Andrieux, François Berger, Jean-Paul Issartel, Didier Wion

To cite this version:

Marie-France Nissou, Jacques Brocard, Michèle El Atifi, Audrey Guttin, Annie Andrieux, et al.. The transcriptomic response of mixed neuron-glial cell cultures to 1,25-dihydroxyvitamin d3 includes genes limiting the progression of neurodegenerative diseases.. Journal of Alzheimer’s Disease, IOS Press, 2013, 35 (3), pp.553-64. �10.3233/JAD-122005�. �inserm-00838410�

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and behaviour [25-29]. In addition the vitamin D prohormone or the 1,25D3 hormone have neuroprotective effects in several rodent experimental models of disease or injury including Alzheimer’s disease [30], Parkinson’s disease [31,32,33], traumatic brain injury [34-37], multiple sclerosis and demyelination [38-43]. A possible drawback of these in vivo experimental models is linked to the extreme complexity of the vitamin D endocrine system which encompasses many different physiological functions. Hence, some behavioural effects observed in vivo with vitamin D deficiency or knock out experimental models might be indirect and related for example to some effects of vitamin D depletion on bone and muscle [44]. In addition to these in vivo studies, the effects of vitamin D on nervous system have also been investigated in vitro on glial or neuronal cell cultures. For example 1,25D3 regulates the expression of VDR, and2 13EDB8FE6E921 32 3:DB8A675 (Cyp24A) in astrocytes [45,46]. 1,25D3 also regulates the expression of VDR in oligodendrocytes, Schwann cell and cortical neuron cultures [47-49]. However, a consequence of using pure cell cultures, either glial or neuronal, is the disruption of the paracrine interactions existing between these

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different cell types in brain tissue. Such interactions can be highly relevant for understanding 1,25D3 function in the nervous system. Therefore, a complementary experimental approach is to study the effect of 1,25D3 treatment on mixed brain cell population. As vitamin D deficiency during pregnancy affects brain development [21], we used in the present study neuron-glial mixed cell cultures issued from neural stem cell cultures. In view of the prevalence of chronic or circannual vitamin D deficiency and/or insufficiency in human [1], the aim of this study was to characterize the transcriptomic response of mixed brain neuron-glial cell cultures issued from neural stem cells and chronically exposed to 1,25D3 to determine if this response includes genes related to neurodegenerative or psychiatric disease.2

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ACTB ACCAGAGGCATACAGGGACA CTAAGGCCAACCGTGAAAAG

CAR14 GTTTCCCAGCCGCTTCTT TGGGTCTAGGTGTGGGAATC

CBS GCAGTGACAACCCCAAACA GCCTGGTCAGGAGTGGTG

CRABP1 TGTGCAGTGAATCTTGTTCTCA AAGGTCGGAGAGGGCTTC

CYP24a1 TCTTGATTTGGGGGTGAAAA CTGCCATTGCGTTCTGT

DIO2 GGAATTGGGAGCATCTTCAC CTGCGCTGTGTCTGGAAC

FBLN1 CGGCACTGCTGCTTACAG CAGGACCAGCTAAGATTCCT

GRPR CTTCCGGGATTCGATCTG TGATTCAGAGTGCCTACAATCTTC

ITGA8 AGTTCTGTGCTCCTCTTGGAA TGGAGAATTCACTGGGGACT

ITIH3 CTCTGGGAGGCTCCGTTT CTCTGGCTTGGAGACCTCTG

LCAT GAGGGGGAGAAACAAGTTGA ACACGGCCTGTCATCCTC

NUPR1 GTGTGGTGTCTGTGGTCTGG GAAGCTGCTGACCAAGTTCC

4833424O15Rik GGAGCTAGGTTTCCTGTAACCAC AACCGTCCGATTTCTTGGA

SLC7a3 GAGGAACAGCAGGCACCTT AATTTCTGGGGTCATCTGGA

VDR CTTCTCTGGGGACTCCTCCT TGGACGAGTCCATCATGTCT

Tesc AGGGTTTCCCGAGAGCAG TCACGAAAGGAGAAGCTGAAAT

Cyp24a1 TCTTGATTTGGGGGTGAAAA CTGCCATTGCGTTCTGT

SDHA CAGTTCCACCCCACAGGTA TCTCCACGACACCCTTCTGT

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