Cuprizone-Induced Demyelination in Mouse Hippocampus Is Alleviated by Ketogenic Diet.
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Cuprizone-Induced Demyelination in Mouse Hippocampus Is Alleviated by Ketogenic Diet. / Liu, Chunhong ; Zhang, Ning; Zhang, Ruiyan ; Jin, Li ; Petridis , Athanasios K ; Loers, Gabriele; Zheng, Xuexing ; Wang, Zhengping ; Siebert, Hans-Christian .
in: J AGR FOOD CHEM, Jahrgang 68, Nr. 40, 07.10.2020, S. 11215–11228.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Cuprizone-Induced Demyelination in Mouse Hippocampus Is Alleviated by Ketogenic Diet.
AU - Liu, Chunhong
AU - Zhang, Ning
AU - Zhang, Ruiyan
AU - Jin, Li
AU - Petridis , Athanasios K
AU - Loers, Gabriele
AU - Zheng, Xuexing
AU - Wang, Zhengping
AU - Siebert, Hans-Christian
PY - 2020/10/7
Y1 - 2020/10/7
N2 - Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Recently, ketogenic diet (KD) supplementation has attracted great interest. Therefore, we established the cuprizone (CPZ)-induced demyelination mouse model to investigate the possible neuroprotective effect of KD on the hippocampus of mice. We found that KD significantly elevated the level of serum β-hydroxybutyric acid, improved behavioral and motor abnormalities, and impaired the spatial learning and memory of CPZ-induced demyelination mice. Meanwhile, KD lessened the hippocampal demyelination by enhancing the expression of mature oligodendrocytes (OLs), which was revealed by the elevated expression of MBP and CNPase, as well as the luxol fast blue-staining intensity. Furthermore, KD inhibits the activation of microglia (especially M1-like microglia) and reactive astrocytes. Interestingly, KD attenuated the CPZ-induced oxidative stress by decreasing the malondialdehyde (MDA) content and restoring the glutathione (GSH) levels. In addition, the double immunofluorescence staining revealed that KD enhanced the expression of SIRT1 in astrocytes, microglia, and mature oligodendrocytes. Concomitantly, Western blot demonstrated that KD increased the expression of SIRT1, phosphorylated-AKT, mTOR, and PPAR-γ. In conclusion, KD exerted a neuroprotective effect on CPZ-induced demyelination mice, and this activity was associated with the modulation of the SIRT1/PPAR-γ and SIRT1/P-Akt/mTOR pathways.
AB - Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Recently, ketogenic diet (KD) supplementation has attracted great interest. Therefore, we established the cuprizone (CPZ)-induced demyelination mouse model to investigate the possible neuroprotective effect of KD on the hippocampus of mice. We found that KD significantly elevated the level of serum β-hydroxybutyric acid, improved behavioral and motor abnormalities, and impaired the spatial learning and memory of CPZ-induced demyelination mice. Meanwhile, KD lessened the hippocampal demyelination by enhancing the expression of mature oligodendrocytes (OLs), which was revealed by the elevated expression of MBP and CNPase, as well as the luxol fast blue-staining intensity. Furthermore, KD inhibits the activation of microglia (especially M1-like microglia) and reactive astrocytes. Interestingly, KD attenuated the CPZ-induced oxidative stress by decreasing the malondialdehyde (MDA) content and restoring the glutathione (GSH) levels. In addition, the double immunofluorescence staining revealed that KD enhanced the expression of SIRT1 in astrocytes, microglia, and mature oligodendrocytes. Concomitantly, Western blot demonstrated that KD increased the expression of SIRT1, phosphorylated-AKT, mTOR, and PPAR-γ. In conclusion, KD exerted a neuroprotective effect on CPZ-induced demyelination mice, and this activity was associated with the modulation of the SIRT1/PPAR-γ and SIRT1/P-Akt/mTOR pathways.
U2 - 10.1021/acs.jafc.0c04604
DO - 10.1021/acs.jafc.0c04604
M3 - SCORING: Journal article
C2 - 32921051
VL - 68
SP - 11215
EP - 11228
JO - J AGR FOOD CHEM
JF - J AGR FOOD CHEM
SN - 0021-8561
IS - 40
ER -