Sodium Benzoate, a Metabolite of Cinnamon and a Food Additive, Upregulates Ciliary Neurotrophic Factor in Astrocytes and Oligodendrocytes
- 398 Downloads
Ciliary neurotrophic factor (CNTF) is a promyelinating trophic factor that plays an important role in multiple sclerosis (MS). However, mechanisms by which CNTF expression could be increased in the brain are poorly understood. Recently we have discovered anti-inflammatory and immunomodulatory activities of sodium benzoate (NaB), a metabolite of cinnamon and a widely-used food additive. Here, we delineate that NaB is also capable of increasing the mRNA and protein expression of CNTF in primary mouse astrocytes and oligodendrocytes and primary human astrocytes. Accordingly, oral administration of NaB and cinnamon led to the upregulation of astroglial and oligodendroglial CNTF in vivo in mouse brain. Induction of experimental allergic encephalomyelitis, an animal model of MS, reduced the level of CNTF in the brain, which was restored by oral administration of cinnamon. While investigating underlying mechanisms, we observed that NaB induced the activation of protein kinase A (PKA) and H-89, an inhibitor of PKA, abrogated NaB-induced expression of CNTF. The activation of cAMP response element binding (CREB) protein by NaB, the recruitment of CREB and CREB-binding protein to the CNTF promoter by NaB and the abrogation of NaB-induced expression of CNTF in astrocytes by siRNA knockdown of CREB suggest that NaB increases the expression of CNTF via the activation of CREB. These results highlight a novel myelinogenic property of NaB and cinnamon, which may be of benefit for MS and other demyelinating disorders.
KeywordsSodium benzoate CNTF Astrocytes Oligodendrocytes PKA CREB
This study was supported by National Institutes of Health Grant (AT6681) and Veteran Affairs Merit Award (I01BX002174).
- 9.Kuhlmann T, Remington L, Cognet I, Bourbonniere L, Zehntner S, Guilhot F, Herman A, Guay-Giroux A, Antel JP, Owens T, Gauchat JF (2006) Continued administration of ciliary neurotrophic factor protects mice from inflammatory pathology in experimental autoimmune encephalomyelitis. Am J Pathol 169:584–598CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Aebischer P, Schluep M, Deglon N, Joseph JM, Hirt L, Heyd B, Goddard M, Hammang JP, Zurn AD, Kato AC, Regli F, Baetge EE (1996) Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients. Nat Med 2:696–699CrossRefPubMedGoogle Scholar
- 25.Jana M, Pahan K (2013) Down-regulation of myelin gene expression in human oligodendrocytes by nitric oxide: implications for demyelination in multiple sclerosis. J Clin Cell Immunol 4Google Scholar
- 36.Ghosh A, Corbett GT, Gonzalez FJ, Pahan K (2012) Gemfibrozil and fenofibrate, FDA-approved lipid-lowering drugs, upregulate tripeptidyl-peptidase 1 in brain cells via peroxisome proliferator-activated receptor-a: implications for late infantile neuronal ceroid lipofuscinosis therapy. J Biol Chem 287:38922–38935CrossRefPubMedPubMedCentralGoogle Scholar