Analysis Tools
mortality/aging
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• pups die within 0-7 days after birth
• daily oral gavage of nicotinamide riboside (vitamin B3) dosing starting 2 days after birth yields no improvement in survival
• daily intraperitoneal dosing of nicotinamide riboside (vitamin B3) at P0 results in improvement of survival
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• pups die within 0-7 days after birth
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• homozygous embryos from heterozygous mothers bred with heterozygous males and fed a vitamin B3-deficient diet die in utero, with no pups born
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growth/size/body
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• mice show stunted growth after birth
• most mice treated with vitamin B3 show rescue of low body weight
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nervous system
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• cell death is seen in several brain regions, including the cortex and striatum, at P5
• TUNEL staining shows cell death in the same cortical regions showing serine and glutathione loss
• daily intraperitoneal dosing of vitamin B3 at P0 results in improvement of the cell death seen in the brain
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• Iba1 staining shows microglial activation in the same cortical regions showing serine and glutathione loss
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• neuroinflammation is seen in several brain regions, including the cortex and striatum, at P5
• most mice treated with vitamin B3 show rescue of neuropathology
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integument
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• mice with scaly skin show decreased subcutaneous adiposity
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• mice with scaly skin show decreased dermal thickness
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scaly skin
(
J:389717
)
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• some mice that survive long enough show scaly skin
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homeostasis/metabolism
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• glutathione is reduced in the brain, most evident in the cortex
• primary brain endothelial cells from P5 mice show depletion of glutathione
• glutathione levels are fully restored by daily vitamin B3 treatment
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• serine and phosphoserine levels are reduced throughout the brain, with cortical regions showing the greatest depletion
• daily vitamin B3 treatment rescues brain serine levels
• primary brain endothelial cells from P5 mice show depletion of serine
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• serine levels are lower in the plasma
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• accumulation of the error metabolites NADHX (6-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide) and cyclic NADHX across all tissues at P5
• depletion of the active form of vitamin B3, NAD(H) (nicotinamide adenine dinucleotide), in brain and skin, but not in the liver, heart, or kidney, at P5
• daily vitamin B3 treatment rescues brain NAD(H) levels
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• primary brain endothelial cells from P5 mice show depletion of serine, glutathione, and nucleotides, indicating impaired one-carbon metabolism and redox homeostasis
• brain-wide depletion of cyclic ADP-ribose, a metabolite directly derived from NAD+, at P5
• depletion of cyclic ADP-ribose in the brain is fully reversed by daily vitamin B3 treatment
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immune system
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• Iba1 staining shows microglial activation in the same cortical regions showing serine and glutathione loss
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• neuroinflammation is seen in several brain regions, including the cortex and striatum, at P5
• most mice treated with vitamin B3 show rescue of neuropathology
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hematopoietic system
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• Iba1 staining shows microglial activation in the same cortical regions showing serine and glutathione loss
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adipose tissue
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• mice with scaly skin show decreased subcutaneous adiposity
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cellular
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• cell death is seen in several brain regions, including the cortex and striatum, at P5
• TUNEL staining shows cell death in the same cortical regions showing serine and glutathione loss
• daily intraperitoneal dosing of vitamin B3 at P0 results in improvement of the cell death seen in the brain
|
|
• Iba1 staining shows microglial activation in the same cortical regions showing serine and glutathione loss
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