Effects of creatine treatment on survival and differentiation of GABA-ergic neurons in cultured striatal tissue

Autor: Andres, Robert, Ducray, Angélique, Huber, Alexander, Pérez-Bouza, Alberto, Krebs, Sandra, Schlattner, Uwe, Seiler, Rolf, Wallimann, Theo, Widmer, Hans Rudolf
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, Hamant, Sarah, Universität Bern [Bern] (UNIBE)
Jazyk: angličtina
Rok vydání: 2005
Předmět:
MESH: Cell Differentiation
MESH: Rats
Cell Survival
Neurotoxins
MESH: Neurons
MESH: Stem Cells
MESH: gamma-Aminobutyric Acid
MESH: Drug Administration Schedule
Culture Media
Serum-Free
Drug Administration Schedule
MESH: Corpus Striatum
MESH: Dose-Response Relationship
Drug
Phosphatidylinositol 3-Kinases
MESH: Propionic Acids
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology
Animals
Tissue Distribution
MESH: Animals
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
Rats
Wistar
MESH: Tissue Distribution
Creatine Kinase
Cells
Cultured
gamma-Aminobutyric Acid
MESH: Neurotoxins
Neurons
MESH: Creatine Kinase
Dose-Response Relationship
Drug
MESH: Creatine
Stem Cells
Cell Differentiation
MESH: 1-Phosphatidylinositol 3-Kinase
MESH: Rats
Wistar
Creatine
Nitro Compounds
MESH: Culture Media
Serum-Free
MESH: Mitogen-Activated Protein Kinases
Corpus Striatum
MESH: Nitro Compounds
Rats
Isoenzymes
MESH: Glucose
Glucose
nervous system
MESH: Cell Survival
MESH: Isoenzymes
Mitogen-Activated Protein Kinases
Propionates
MESH: Cells
Cultured
Zdroj: Journal of Neurochemistry
Journal of Neurochemistry, Wiley, 2005, 95 (1), pp.33-45. ⟨10.1111/j.1471-4159.2005.03337.x⟩
ISSN: 0022-3042
1471-4159
Popis: International audience; Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder, characterized by a prominent loss of GABA-ergic medium-sized spiny neurons in the caudate putamen. There is evidence that impaired energy metabolism contributes to neuronal death in HD. Creatine is an endogenous substrate for creatine kinases and thereby supports cellular ATP levels. This study investigated the effects of creatine supplementation (5 mm) on cell survival and neuronal differentiation in striatal cultures. Chronic creatine treatment resulted in significant increased densities of GABA-immunoreactive (-ir) neurons, although total neuronal cell number and general viability were not affected. Similar effects were seen after short-term treatment, suggesting that creatine acted as a differentiation factor. Inhibitors of transcription or translation did not abolish the creatine-mediated effects, nor did omission of extracellular calcium, whereas inhibition of mitogen-activated protein kinase and phosphatidylinositol-3-kinase significantly attenuated the creatine induced increase in GABA-ir cell densities. Creatine exhibited significant neuroprotection against toxicity instigated either by glucose- and serum deprivation or addition of 3-nitropropionic acid. In sum, the neuroprotective properties in combination with promotion of neuronal differentiation suggest that creatine has potential as a therapeutic drug in the treatment of neurodegenerative diseases, like HD.
Databáze: OpenAIRE
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