Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Andres, RH; Ducray, AD; Huber, AW; Pérez-Bouza, A; Krebs, SH; Schlattner, U; Seiler, RW; Wallimann, T; Widmer, HR.
Effects of creatine treatment on survival and differentiation of GABA-ergic neurons in cultured striatal tissue.
J Neurochem. 2005; 95(1):33-45
Doi: 10.1111/j.1471-4159.2005.03337.x
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Huber Sandra
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cell Differentiation - drug effects
- Cell Survival - drug effects
- Cells, Cultured -
- Corpus Striatum - cytology
- Corpus Striatum - metabolism
- Creatine - administration & dosage
- Creatine - pharmacology
- Creatine Kinase - metabolism
- Culture Media, Serum-Free - pharmacology
- Dose-Response Relationship, Drug -
- Drug Administration Schedule -
- Glucose - deficiency
- Isoenzymes - metabolism
- Mitogen-Activated Protein Kinases - metabolism
- Neurons - cytology
- Neurons - metabolism
- Neurotoxins - pharmacology
- Nitro Compounds -
- Phosphatidylinositol 3-Kinases - metabolism
- Propionates - pharmacology
- Rats -
- Rats, Wistar -
- Stem Cells - cytology
- Stem Cells - metabolism
- Tissue Distribution -
- gamma-Aminobutyric Acid - metabolism
- Find related publications in this database (Keywords)
- creatine
- creatine kinase
- differentiation
- GABA
- ganglionic eminence
- neuroprotection