Deletion of CD38 Suppresses Glial Activation and Neuroinflammation in a Mouse Model of Demyelination

CD38 is an enzyme that catalyzes the synthesis of cyclic adenosine diphosphate-ribose from nicotinamide adenine dinucleotide (NAD ). We recently reported that this molecule regulates the maturation and differentiation of glial cells such as astrocytes and oligodendrocytes (OLs) in the developing bra...

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Bibliographic Details
Published in:Frontiers in cellular neuroscience 2019-06, Vol.13, p.258-258
Main Authors: Roboon, Jureepon, Hattori, Tsuyoshi, Ishii, Hiroshi, Takarada-Iemata, Mika, Le, Thuong Manh, Shiraishi, Yoshitake, Ozaki, Noriyuki, Yamamoto, Yasuhiko, Sugawara, Akira, Okamoto, Hiroshi, Higashida, Haruhiro, Kitao, Yasuko, Hori, Osamu
Format: Article
Language:English
Subjects:
Adenine
Apoptosis
Astrocytes
Biochemistry
Brain
CD38 antigen
Cell differentiation
Clonal deletion
Cuprizone
Demyelination
Glial cells
gliosis
Inflammation
Microglia
Multiple sclerosis
Myelin
NAD
Neurodegeneration
neuroinflammation
Neuronal-glial interactions
Neuroscience
Nicotinamide
Oligodendrocytes
Phagocytosis
Polymerase chain reaction
Ribose
Rodents
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Summary:CD38 is an enzyme that catalyzes the synthesis of cyclic adenosine diphosphate-ribose from nicotinamide adenine dinucleotide (NAD ). We recently reported that this molecule regulates the maturation and differentiation of glial cells such as astrocytes and oligodendrocytes (OLs) in the developing brain. To analyze its role in the demyelinating situation, we employed cuprizone (CPZ)-induced demyelination model in mice, which is characterized by oligodendrocyte-specific apoptosis, followed by the strong glial activation, demyelination, and repopulation of OLs. By using this model, we found that CD38 was upregulated in both astrocytes and microglia after CPZ administration. Experiments using wild-type and CD38 knockout (KO) mice, together with those using cultured glial cells, revealed that CD38 deficiency did not affect the initial decrease of the number of OLs, while it attenuated CPZ-induced demyelination, and neurodegeneration. Importantly, the clearance of the degraded myelin and oligodendrocyte repopulation were also reduced in CD38 KO mice. Further experiments revealed that these observations were associated with reduced levels of glial activation and inflammatory responses including phagocytosis, most likely through the enhanced level of NAD in CD38-deleted condition. Our results suggest that CD38 and NAD in the glial cells play a critical role in the demyelination and subsequent oligodendrocyte remodeling through the modulation of glial activity and neuroinflammation.
ISSN:1662-5102
1662-5102
DOI:10.3389/fncel.2019.00258