Creatine and Cyclocreatine Attenuate MPTP Neurotoxicity

Matthews, Russell T.; Ferrante, Robert J.; Klivényi, Péter; Yang, Le; Klein, Autumn; Mueller, Gerald; Kaddurah‐Daouk, Rima; Beal, M. Flint

doi:10.1006/exnr.1999.7049

Cited by 345 publications

(213 citation statements)

References 38 publications

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“…(1 rev/min) rotating roller-drum (36) placed in an incubator at 37°C in a 5% CO 2 atmosphere as described in 7,23,57,58).…”

Section: Introductionmentioning

confidence: 99%

“…In line with these notions, recent studies demonof culture medium consisting of 55% DMEM, 32.5% Hank's balanced salt solution (HBSS; Gibco), 0.3% glustrated a neuroprotective effect of creatine supplementation in a variety of experimental models of neurological cose, 10% fetal calf serum (FCS; Gibco), and 1% 0.01 M HEPES (Merck). The tubes were placed in a slowly disorders including PD, Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and ischemia (2,6,(1 rev/min) rotating roller-drum (36) placed in an incubator at 37°C in a 5% CO 2 atmosphere as described in 7,23,57,58).Knowledge on the functional effects of the creatine detail previously (89). The culture tubes were randomly assigned to either the creatine-treated or to the control kinase/phosphocreatine system regarding the metabolism of embryonic neurons is limited.…”

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confidence: 99%

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Creatine Supplementation Improves Dopaminergic Cell Survival and Protects against MPP+ Toxicity in an Organotypic Tissue Culture System

et al. 2005

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Cell replacement therapy using mesencephalic precursor cells is an experimental approach for the treatment of Parkinson's disease (PD). A significant problem associated with this procedure is the poor survival of grafted neurons. Impaired energy metabolism is considered to contribute to neuronal cell death after transplantation. Creatine is a substrate for mitochondrial and cytosolic creatine kinases (CK) and buffers cellular ATP resources. Furthermore, elevated cellular creatine levels facilitate metabolic channeling and show antiapoptotic properties. Exogenous creatine supplementation therefore might offer a tool for improvement of dopaminergic neuron survival. The present study aimed at investigating the effects of creatine on cell survival of rat embryonic day 14 (E14) ventral mesencephalic neurons grown as organotypic free-floating roller tube (FFRT) cultures. We found that the brain-specific isoform of CK (BB-CK) and the ubiquitous mitochondrial isoform (uMt-CK) are expressed at high levels in FFRT cultures and colocalize with tyrosine hydroxylase immunoreactive (TH-ir) cells. Exposure of these cultures to creatine induced an increase in the content of the BB-CK isotype. Creatine (5 mM) administration starting at day in vitro (DIV) 7 resulted in a significant increase (+35%) in TH-ir cell density at DIV21. In addition, we observed that creatine treatment provided neuroprotection against 1-methyl-4-phenyl pyridinium ion (MPP + )-induced TH-ir cell loss in the FFRT culture system, resulting in a significantly higher density (+19%) of TH-ir neurons in creatine-treated cultures compared to corresponding controls. The decrease of TH-ir neurons in the MPP + -treated group corresponded with an increase in immunoreactivity for active caspase-3, an effect that was not seen in the group receiving creatine supplementation. In conclusion, our data imply that creatine administration is beneficial for the survival of TH-ir neurons encountering harmful conditions. Key words: Ventral mesencephalic cell cultures; Creatine; Tyrosine hydroxylase; Free-floating roller tubes; MPP + ; Parkinson's disease INTRODUCTIONmal metabolic conditions are required during the in vitro storage period to prevent cell loss due to metabolic and oxidative stress (88). Furthermore, release of toxic meTransplantation of embryonal ventral mesencephalic cells is an experimental therapy for the treatment of tabolites and neurotransmitters with excitotoxic potential, such as dopamine (10) and glutamate (33), from medically intractable Parkinson's disease (PD) and has been shown to be effective in reinnervating the host stridying cells contributes to an unfavorable environment and potentiate cell death (79). So far, culture conditions atum (31,32,54,69). However, limited availability of human embryonal tissue originating from legal abortions, are still suboptimal compared to the in vivo environment, resulting in an unsatisfactory survival of dopaminethical concerns, and the poor survival of the grafts impair a widespread clinical application. Collecti...

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“…(1 rev/min) rotating roller-drum (36) placed in an incubator at 37°C in a 5% CO 2 atmosphere as described in 7,23,57,58).…”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Creatine Supplementation Improves Dopaminergic Cell Survival and Protects against MPP+ Toxicity in an Organotypic Tissue Culture System

et al. 2005

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“…Thus, therapies targeting mitochondrial bioenergetics and oxidative stress pathways could have neuroprotective effect and would be able to improve the seizure activity and attenuate the severity of epilepsy. Administration of creatine is frequently used and has been shown to protect brain injury in animal models of ALS, Huntington's disease and MPTP-induced Parkinsonism (Ferrante et al, 2000;Matthews et al, 1999). Creatine can move through blood to brain and increase the pool of phosphocreatine/creatine by mitochondrial creatine kinase to boost the neuronal energy level.…”

Section: Therapeutic Approaches To Target Mitochondrial Bioenergeticsmentioning

confidence: 99%

The Cross-Talk Between Mitochondria and the Nucleus in the Response to Oxidative Stress Associated with Mitochondrial Dysfunction in Mitochondrial Encephalomyopathies

Wu¹,

Lee²,

Wu³

et al. 2011

Underlying Mechanisms of Epilepsy

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“…Creatine (CRT) exerts neuroprotective effects in vivo against various neurotoxins and in transgenic mouse models of both amyotrophic lateral sclerosis (ALS) and Huntington's disease [14][15][16]. The mitochondrial dysfunction and energy deficit have been well demonstrated in all neurodegenerative disorders, including PD.…”

Section: Creatinementioning

confidence: 99%