title: Sodium Benzoate, a Metabolite of Cinnamon and a Food Additive, Upregulates Ciliary Neurotrophic Factor in Astrocytes and Oligodendrocytes.
abstract: 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.
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, 1735 West Harrison St, Suite Cohn 320, Chicago, IL, 60612, USA.
authors.forename: Khushbu K
authors.initials: KK
authors.lastname: Modi
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, 1735 West Harrison St, Suite Cohn 320, Chicago, IL, 60612, USA.
authors.forename: Malabendu
authors.initials: M
authors.lastname: Jana
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, 1735 West Harrison St, Suite Cohn 320, Chicago, IL, 60612, USA.
authors.forename: Susanta
authors.initials: S
authors.lastname: Mondal
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, 1735 West Harrison St, Suite Cohn 320, Chicago, IL, 60612, USA. Kalipada_Pahan@rush.edu.|Division of Research and Development, Jesse Brown Veterans Affairs Medical Center, 820 South Damen Avenue, Chicago, IL, USA. Kalipada_Pahan@rush.edu.
authors.forename: Kalipada
authors.initials: K
authors.lastname: Pahan
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D020934:Ciliary Neurotrophic Factor / Q000096:biosynthesis*; D002935:Cinnamomum zeylanicum / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis / Q000235:genetics; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D005520:Food Preservatives / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism*; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020160:Sodium Benzoate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D020934:Ciliary Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D005520:Food Preservatives; D007546:Isoquinolines; D012333:RNA, Messenger; D013449:Sulfonamides; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D020160:Sodium Benzoate
keywords: Astrocytes; CNTF; CREB; Oligodendrocytes; PKA; Sodium benzoate