Stimulation of Dopamine Production by Sodium Benzoate, a Metabolite of Cinnamon and a Food Additive

被引:8
作者
Rangasamy, Suresh B. [1 ,2 ]
Dasarathi, Sridevi [2 ]
Nutakki, Aparna [2 ]
Mukherjee, Shreya [2 ]
Nellivalasa, Rohith [2 ]
Pahan, Kalipada [1 ,2 ]
机构
[1] Jesse Brown Vet Affairs Med Ctr, Div Res & Dev, Chicago, IL USA
[2] Rush Univ, Dept Neurol Sci, Med Ctr, 1735 West Harrison St,Suite Cohn 310, Chicago, IL 60612 USA
关键词
A53T; CREB; dopamine; sodium benzoate; striatum; substantia nigra pars compacta; tyrosine hydroxylase; LIPID-LOWERING DRUG; KAPPA-B ACTIVATION; PARKINSONS-DISEASE; MOUSE MODEL; UP-REGULATION; ADOPTIVE TRANSFER; T-CELLS; NEURONS; PATHOGENESIS; GEMFIBROZIL;
D O I
10.3233/ADR-210001
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: Parkinson's disease (PD) is one of the most important neurodegenerative disorders in human in which recovery of functions could be achieved by improving the survival and function of residual dopaminergic neurons in the substantia nigra pars compacta. Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the dopamine (DA) biosynthesis pathway. Objective: Earlier our laboratory has shown that sodium benzoate (NaB), a metabolite of cinnamon and an FDA-approved drug against urea cycle disorders and glycine encephalopathy, increases neuroprotective molecules and protects dopaminergic neurons in a mouse model of PD. Here, we examined whether NaB could stimulate the production of DA in dopaminergic neurons. Methods: We employed PCR, real-time PCR, western blot, immunostaining, and HPLC to study the signature function of dopaminergic neurons. Locomotor functions were monitored in mice by open-field. Results: NaB increased the mRNA and protein expression of TH to produce DA in mouse MN9D dopaminergic neuronal cells. Accordingly, oral feeding of NaB increased the expression of TH in the nigra, upregulated striatal DA, and improved locomotor activities in striatum of normal C57/BL6 and aged A53T-alpha-syn transgenic mice. Rapid induction of cAMP response element binding (CREB) activation by NaB in dopaminergic neuronal cells and the abrogation of NaB-induced expression of TH by siRNA knockdown of CREB suggest that NaB stimulates the transcription of TH in dopaminergic neurons via CREB. Conclusion: These results indicate a new function of NaB in which it may be beneficial in PD via stimulation of DA production from residual dopaminergic neurons.
引用
收藏
页码:295 / 310
页数:16
相关论文
共 34 条
[1]   Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease [J].
Benner, EJ ;
Mosley, RL ;
Destache, CJ ;
Lewis, TB ;
Jackson-Lewis, V ;
Gorantla, S ;
Nemachek, C ;
Green, SR ;
Przedborski, S ;
Gendelman, HE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (25) :9435-9440
[2]   Sodium benzoate, a food additive and a metabolite of cinnamon, modifies T cells at multiple steps and inhibits adoptive transfer of experimental allergic encephalomyelitis [J].
Brahmachari, Saurav ;
Pahan, Kalipada .
JOURNAL OF IMMUNOLOGY, 2007, 179 (01) :275-283
[3]   Sodium Benzoate, a Metabolite of Cinnamon and a Food Additive, Reduces Microglial and Astroglial Inflammatory Responses [J].
Brahmachari, Saurav ;
Jana, Arundhati ;
Pahan, Kalipada .
JOURNAL OF IMMUNOLOGY, 2009, 183 (09) :5917-5927
[4]   Gemfibrozil, a Lipid-Lowering Drug, Upregulates IL-1 Receptor Antagonist in Mouse Cortical Neurons: Implications for Neuronal Self-Defense [J].
Corbett, Grant T. ;
Roy, Avik ;
Pahan, Kalipada .
JOURNAL OF IMMUNOLOGY, 2012, 189 (02) :1002-1013
[5]   Role of very-late antigen-4 (VLA-4) in myelin basic protein-primed T cell contact-induced expression of proinflammatory cytokines in microglial cells [J].
Dasgupta, S ;
Jana, M ;
Liu, XJ ;
Pahan, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (25) :22424-22431
[6]   Parkinson's disease: Mechanisms and models [J].
Dauer, W ;
Przedborski, S .
NEURON, 2003, 39 (06) :889-909
[7]   Selective inhibition of NF-κB activation prevents dopaminergic neuronal loss in a mouse model of Parkinson's disease [J].
Ghosh, Anamitra ;
Roy, Avik ;
Liu, Xiaojuan ;
Kordower, Jeffrey H. ;
Mufson, Elliott J. ;
Hartley, Dean M. ;
Ghosh, Sankar ;
Mosley, R. Lee ;
Gendelman, Howard E. ;
Pahan, Kalipada .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (47) :18754-18759
[8]   Gemfibrozil, a Lipid-lowering Drug, Induces Suppressor of Cytokine Signaling 3 in Glial Cells IMPLICATIONS FOR NEURODEGENERATIVE DISORDERS [J].
Ghosh, Arunava ;
Pahan, Kalipada .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (32) :27189-27203
[9]   Neurological implications of urea cycle disorders [J].
Gropman, A. L. ;
Summar, M. ;
Leonard, J. V. .
JOURNAL OF INHERITED METABOLIC DISEASE, 2007, 30 (06) :865-879
[10]   Up-Regulation of Neurotrophic Factors by Cinnamon and its Metabolite Sodium Benzoate: Therapeutic Implications for Neurodegenerative Disorders [J].
Jana, Arundhati ;
Modi, Khushbu K. ;
Roy, Avik ;
Anderson, John A. ;
van Breemen, Richard B. ;
Pahan, Kalipada .
JOURNAL OF NEUROIMMUNE PHARMACOLOGY, 2013, 8 (03) :739-755