Table 1.
BBB (see Supplementary Table 3) | Pericytes (see Supplementary Table 4) | Astrocytes (see Supplementary Table 5) | Microglia (see Supplementary Table 6) | Oligodendrocytes (see Supplementary Table 7) | |
---|---|---|---|---|---|
VitD metabolism | |||||
VDR | ↑ in vitro118,119 n.s. in vitro120,121 ↑ in vivo122,123 |
↑ in vitro124,125 | ↑ in vitro126–128 n.s. in vitro121 |
↑ in vitro121,129–131 | ↑ in vitro132–134 |
Cyp24a1 | ↑ in vitro118 n.s. in vitro121 ↑ in vivo135,136 |
↑ in vitro121,127 | ↑ in vitro121,127,129 | ||
Cyp24b1 | n.s. in vitro121,127 | ||||
Growth factors | |||||
BDNF | ↑ in vivo137,138 | ||||
NGF | ↑ in vitro139,140 | ||||
Signalling | |||||
p-AKT | ↑ in vitro141,142 | ||||
p-ERK | ↑ in vitro141,142 | ||||
NF-kb Activation | ↓ in vitro143,144 | ||||
Cell viability | ↑ in vitro141,144 | n.s. in vitro145–147 ↑ in vitro148 |
|||
Leakage | |||||
Claudin-5 | ↑ in vitro143,144 | ||||
ZO-1 | ↑ in vitro143,144 ↑ in vivo149,150 |
||||
TEER | ↑ in vitro143,144 | ||||
Brain efflux | ↑ in vivo135,151 | ||||
Permeability | ↓ in vivo26,122,137,138,149,150 | ||||
Trafficking | |||||
Mrp1 | n.s. in vivo120,152 | ||||
P-gP | ↑ in vivo120,135,136,151,152 | ||||
BCRP | n.s. in vivo135,136 | ||||
Oxidative stress | |||||
NO-production | ↑ in vitro141,142 | ↓ in vitro145,147,148,153 n.s. in vitro154 |
|||
ROS production | ↓ in vitro141,142 | ||||
iNOS | ↓ in vitro129,131,148,155 n.s. in vitro153 |
||||
SOD | ↑ in vivo137,156 | ||||
Arg1 | ↑ in vitro131,155 | ||||
Cytokines | |||||
IL-10 | ↑ in vitro129,130 | ||||
TNFa | ↓ in vitro131,145,147,153,154 n.s. in vitro148,155 ↓ in vivo157,158 |
||||
IL-1b | ↓ in vitro131,148,155 | ||||
IL-6 | ↓ in vitro129,131,147,148,153–155 | ||||
Myelin | |||||
Myelination | ↑ in vivo34,159 | ||||
MBP | ↑ in vivo159,160 | ||||
Demyelination | ↓ in vivo34,159–162 | ||||
CNS insult | |||||
Osteopontin | ↑ in vivo122,123 | ||||
GFAP | ↓ in vivo163–166 ↑ in vivo161,167,168 n.s. in vivo169 |
||||
Radio clinical parameters | |||||
Brain oedema | ↓ in vivo122,137,150 | ||||
Neurological deficit | ↓ in vivo122,137,150 n.s. in vivo170 |
||||
New Gd-enhancing lesions | ↓ multiple sclerosis Patients171–173 n.s. multiple sclerosis patients86 |
Molecules/mechanisms/endpoints showing concordant variation after VitD stimulation in more than one study for each cell types are represented in this table. See Supplementary Tables 3–7 for experimental details. Arg1, Arginase-1; BBB, blood–brain barrier; BCRP, breast cancer resistance protein; BDNF, brain-derived neurotrophic factor; GFAP, glial fibrillary acidic protein; IL, interleukin; iNOS, inducible nitric oxide synthase; MBP, myelin basic protein; Mrp1, multidrug resistance-associated protein 1; NGF, neural growth factor; NO, nitric oxide; P-gP, permeability-glycoprotein; ROS, reactive oxygen species; SOD, superoxide dismutase; TEER, transepithelial/trans-endothelial electrical resistance; TNF-a, tumour necrosis factor alpha; VDR, vitamin D receptor.