Effects of creatine treatment on the survival of dopaminergic neurons in cultured fetal ventral mesencephalic tissue

Autor: Alexander W. Huber, Alberto Pérez-Bouza, Hans Rudolf Widmer, Uwe Schlattner, Theo Wallimann, Sandra H. Krebs, Rolf W. Seiler, Robert H. Andres
Přispěvatelé: Department of Neurosurgery, Université de Berne, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Department of Biology, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)-Institute of Cell Biology, Universität Bern [Bern] (UNIBE), Hamant, Sarah
Rok vydání: 2005
Předmět:
1-Methyl-4-phenylpyridinium
Dopamine
MESH: Drug Interactions
Creatine Kinase
Mitochondrial Form
MESH: Neurons
MESH: Rats
Sprague-Dawley
Rats
Sprague-Dawley
chemistry.chemical_compound
MESH: Pregnancy
0302 clinical medicine
Mesencephalon
Pregnancy
Drug Interactions
MESH: Animals
Creatine Kinase
MESH: Tyrosine 3-Monooxygenase
Cells
Cultured
MESH: 1-Methyl-4-phenylpyridinium
Neurons
0303 health sciences
MESH: Creatine Kinase
MESH: Creatine
General Neuroscience
Dopaminergic
3. Good health
Isoenzymes
medicine.anatomical_structure
MESH: Cell Survival
Creatinine
MESH: Isoenzymes
Female
MESH: Cells
Cultured
medicine.medical_specialty
Tyrosine 3-Monooxygenase
MESH: Rats
Cell Survival
Substantia nigra
MESH: Dopamine
MESH: Creatinine
Biology
Creatine
Neuroprotection
Phosphocreatine
03 medical and health sciences
Internal medicine
Dopaminergic Cell
Creatine Kinase
BB Form
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology
medicine
Animals
MESH: Cell Shape
MESH: Creatine Kinase
Mitochondrial Form
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
Oxidopamine
Cell Shape
030304 developmental biology
MESH: Sympatholytics
MESH: Creatine Kinase
BB Form
MESH: Mesencephalon
Rats
MESH: Oxidopamine
Endocrinology
nervous system
chemistry
Sympatholytics
biology.protein
Creatine kinase
Neuron
MESH: Female
030217 neurology & neurosurgery
Zdroj: Neuroscience
Neuroscience, Elsevier-International Brain Research Organization, 2005, 133 (3), pp.701-13. ⟨10.1016/j.neuroscience.2005.03.004⟩
ISSN: 0306-4522
1873-7544
DOI: 10.1016/j.neuroscience.2005.03.004
Popis: International audience; Parkinson's disease is a disabling neurodegenerative disorder of unknown etiology characterized by a predominant and progressive loss of dopaminergic neurons in the substantia nigra. Recent findings suggest that impaired energy metabolism plays an important role in the pathogenesis of this disorder. The endogenously occurring guanidino compound creatine is a substrate for mitochondrial and cytosolic creatine kinases. Creatine supplementation improves the function of the creatine kinase/phosphocreatine system by increasing cellular creatine and phosphocreatine levels and the rate of ATP resynthesis. In addition, mitochondrial creatine kinase together with high cytoplasmic creatine levels inhibit mitochondrial permeability transition, a major step in early apoptosis. In the present study, we analyzed the effects of externally added creatine on the survival and morphology of dopaminergic neurons and also addressed its neuroprotective properties in primary cultures of E14 rat ventral mesencephalon. Chronic administration of creatine [5 mM] for 7 days significantly increased survival (by 1.32-fold) and soma size (by 1.12-fold) of dopaminergic neurons, while having no effect on other investigated morphological parameters. Most importantly, concurrent creatine exerted significant neuroprotection for dopaminergic neurons against neurotoxic insults induced by serum and glucose deprivation (P < 0.01), 1-methyl-4-phenyl pyridinium ion (MPP+) [15 microM] and 6-hydroxydopamine (6-OHDA) [90 microM] exposure (P < 0.01). In addition, creatine treatment significantly protected dopaminergic cells facing MPP+-induced deterioration of neuronal morphology including overall process length/neuron (by 60%), number of branching points/neuron (by 80%) and area of influence per individual neuron (by 60%). Less pronounced effects on overall process length/neuron and number of branching points/neuron were also found after 6-OHDA exposure (P < 0.05) and serum/glucose deprivation (P < 0.05). In conclusion, our findings identify creatine as a rather potent natural survival- and neuroprotective factor for developing nigral dopaminergic neurons, which is of relevance for therapeutic approaches in Parkinson's disease and for the improvement of cell replacement strategies.
Databáze: OpenAIRE
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