Ceftriaxone Decreases MPTP-induced Behavioral Disturbances in Animal Model of Parkinson’s disease
International Clinical Neuroscience Journal,
Vol. 3 No. 4 (2016),
7 February 2017
Background and purpose: Progressive degeneration of dopaminergic neurons in the midbrain is the main mechanism of Parkinson’s disease (PD). Recent studies have shown ceftriaxone, a β-lactam antibiotic, to be a neuroprotective in various neurodegenerative disorders. Hence, the present study aimed to investigate the effect of ceftriaxone on behavioral disturbances of PD in an animal model.
Methods: Fifty-six healthy male Wistar rats were selected for this study. They were divided into seven groups according to receiving saline or ceftriaxone, receiving a low or high dose of ceftriaxone and receiving ceftriaxone for short or long periods. Apomorphine-induced rotational test, elevated body swing test and rotarod test were done to examine behavioral performances.
Results: Ceftriaxone can effectively diminish behavioral disturbances induced by MPTP in all behavioral tests. Long administration of ceftriaxone was more effective than short administration in lowering behavioral disturbances. High dose of ceftriaxone was more effective than low dose in initial trials of each behavioral test; however, no difference was observed between them in the last trial.
Conclusion: Results of the current study suggest that ceftriaxone have neuroprotective effects in PD. To obtain a sufficient neuroprotective effect for lowering behavioral disturbances of PD and also preventing side effects of ceftriaxone, long administration of low dose of ceftriaxone seems the best option.
- Parkinson’s disease
- Behavioral tests
How to Cite
Schrag A, Jahanshahi M, Quinn N. What contributes to quality of life in patients with Parkinson's disease? Journal of Neurology, Neurosurgery & Psychiatry. 2000;69(3):308-12.
Levy OA, Malagelada C, Greene LA. Cell death pathways in Parkinson’s disease: proximal triggers, distal effectors, and final steps. Apoptosis. 2009;14(4):478-500.
Ko HS, Lee Y, Shin J-H, Karuppagounder SS, Gadad BS, Koleske AJ, et al. Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function. Proceedings of the National Academy of Sciences. 2010;107(38):16691-6.
Seet RC, Lee C-YJ, Lim EC, Tan JJ, Quek AM, Chong W-L, et al. Oxidative damage in Parkinson disease: measurement using accurate biomarkers. Free Radical Biology and Medicine. 2010;48(4):560-6.
Bronstein JM, Tagliati M, Alterman RL, Lozano AM, Volkmann J, Stefani A, et al. Deep brain stimulation for Parkinson disease: an expert consensus and review of key issues. Archives of neurology. 2011;68(2):165-.
Duker AP, Espay AJ. Surgical treatment of Parkinson disease: past, present, and future. Neurologic clinics. 2013;31(3):799-808.
Aquino CC, Fox SH. Clinical spectrum of levodopa‐induced complications. Movement Disorders. 2015;30(1):80-9.
Verma R, Mishra V, Sasmal D, Raghubir R. Pharmacological evaluation of glutamate transporter 1 (GLT-1) mediated neuroprotection following cerebral ischemia/reperfusion injury. European journal of pharmacology. 2010;638(1):65-71.
Leung T, Lui C, Chen L, Yung W, Chan Y, Yung K. Ceftriaxone ameliorates motor deficits and protects dopaminergic neurons in 6-hydroxydopamine-lesioned rats. ACS chemical neuroscience. 2011;3(1):22-30.
Moriguchi S, Yabuki Y, Fukunaga K. Reduced calcium/calmodulin‐dependent protein kinase II activity in the hippocampus is associated with impaired cognitive function in MPTP‐treated mice. Journal of neurochemistry. 2012;120(4):541-51.
Fujita M, Nishino H, Kumazaki M, Shimada S, Tohyama M, Nishimura T. Expression of dopamine transporter mRNA and its binding site in fetal nigral cells transplanted into the striatum of 6-OHDA lesioned rat. Molecular brain research. 1996;39(1):127-36.
Borlongan CV, Randall TS, Cahill DW, Sanberg PR. Asymmetrical motor behavior in rats with unilateral striatal excitotoxic lesions as revealed by the elevated body swing test. Brain research. 1995;676(1):231-4.
Lundblad M, Vaudano E, Cenci M. Cellular and behavioural effects of the adenosine A2a receptor antagonist KW‐6002 in a rat model of l‐DOPA‐induced dyskinesia. Journal of neurochemistry. 2003;84(6):1398-410.
Rothstein JD, Patel S, Regan MR, Haenggeli C, Huang YH, Bergles DE, et al. β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature. 2005;433(7021):73-7.
Roelcke U, Barnette W, Wilder-Smith E, Sigmund D, Hacke W. Untreated neuroborreliosis: Bannwarth's syndrome evolving into acute schizophrenia-like psychosis. Journal of neurology. 1992;239(3):129-31.
Blum D, Torch S, Lambeng N, Nissou M-F, Benabid A-L, Sadoul R, et al. Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson's disease. Progress in neurobiology. 2001;65(2):135-72.
Albin RL, Greenamyre JT. Alternative excitotoxic hypotheses. Neurology. 1992;42(4):733-.
Haugeto Ø, Ullensvang K, Levy LM, Chaudhry FA, Honoré T, Nielsen M, et al. Brain glutamate transporter proteins form homomultimers. Journal of Biological Chemistry. 1996;271(44):27715-22.
Rothstein JD, Van Kammen M, Levey AI, Martin LJ, Kuncl RW. Selective loss of glial glutamate transporter GLT‐1 in amyotrophic lateral sclerosis. Annals of neurology. 1995;38(1):73-84.
Scott HL, Pow DV, Tannenberg AE, Dodd PR. Aberrant expression of the glutamate transporter excitatory amino acid transporter 1 (EAAT1) in Alzheimer's disease. Journal of Neuroscience. 2002;22(3):RC206: 1-5.
Rao VLR, Bowen KK, Dempsey RJ. Transient focal cerebral ischemia down-regulates glutamate transporters GLT-1 and EAAC1 expression in rat brain. Neurochemical research. 2001;26(5):497-502.
Rothstein JD, Dykes‐Hoberg M, Corson LB, Becker M, Cleveland DW, Price DL, et al. The copper chaperone CCS is abundant in neurons and astrocytes in human and rodent brain. Journal of neurochemistry. 1999;72(1):422-9.
Sepkuty JP, Cohen AS, Eccles C, Rafiq A, Behar K, Ganel R, et al. A neuronal glutamate transporter contributes to neurotransmitter GABA synthesis and epilepsy. The Journal of Neuroscience. 2002;22(15):6372-9.
Miller BR, Dorner JL, Shou M, Sari Y, Barton SJ, Sengelaub DR, et al. Up-regulation of GLT1 expression increases glutamate uptake and attenuates the Huntington's disease phenotype in the R6/2 mouse. Neuroscience. 2008;153(1):329-37.
Sari Y, Prieto AL, Barton SJ, Miller BR, Rebec GV. Ceftriaxone-induced up-regulation of cortical and striatal GLT1 in the R6/2 model of Huntington's disease. Journal of biomedical science. 2010;17(1):1.
Requena JR, Chao C-C, Levine RL, Stadtman ER. Glutamic and aminoadipic semialdehydes are the main carbonyl products of metal-catalyzed oxidation of proteins. Proceedings of the National Academy of Sciences. 2001;98(1):69-74.
Choi J, Sullards MC, Olzmann JA, Rees HD, Weintraub ST, Bostwick DE, et al. Oxidative damage of DJ-1 is linked to sporadic Parkinson and Alzheimer diseases. Journal of Biological Chemistry. 2006;281(16):10816-24.
Tikka T, Usenius T, Tenhunen M, Keinänen R, Koistinaho J. Tetracycline derivatives and ceftriaxone, a cephalosporin antibiotic, protect neurons against apoptosis induced by ionizing radiation. Journal of neurochemistry. 2001;78(6):1409-14.
McBean G. Intrastriatal injection of dl-α-aminoadipate reduces kainate toxicity in vitro. Neuroscience. 1990;34(1):225-34.
Ho S-C, Hsu C-C, Pawlak CR, Tikhonova MA, Lai T-J, Amstislavskaya TG, et al. Effects of ceftriaxone on the behavioral and neuronal changes in an MPTP-induced Parkinson's disease rat model. Behavioural brain research. 2014;268:177-84.
Hsu C-Y, Hung C-S, Chang H-M, Liao W-C, Ho S-C, Ho Y-J. Ceftriaxone prevents and reverses behavioral and neuronal deficits in an MPTP-induced animal model of Parkinson's disease dementia. Neuropharmacology. 2015;91:43-56.
Bisht R, Kaur B, Gupta H, Prakash A. Ceftriaxone mediated rescue of nigral oxidative damage and motor deficits in MPTP model of Parkinson's disease in rats. Neurotoxicology. 2014;44:71-9.
Taherian R, Ahmadi MA. 4-aminopyridine decreases MPTP-induced behavioral disturbances in animal model of Parkinson’s disease. International Clinical Neuroscience Journal. 2016;2(4):142-6.
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