The effects of creatine supplementation on striatal neural progenitor cells depend on developmental stage

Andres, Robert H.; Ducray, Angélique; Andereggen, Lukas; Hohl, Tabea; Schlattner, Uwe; Wallimann, Theo; Widmer, Hans Rudolf (2016). The effects of creatine supplementation on striatal neural progenitor cells depend on developmental stage. Amino acids, 48(8), pp. 1913-1927. Springer 10.1007/s00726-016-2238-8

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Transplantation of neural progenitor cells (NPCs) is a promising experimental therapy for Huntington’s disease (HD). The variables responsible for the success of this approach, including selection of the optimal developmental stage of the grafted cells, are however largely unknown. Supporting cellular energy metabolism by creatine (Cr) supplementation is a clinically translatable method for improving cell transplantation strategies. The present study aims at investigating differences between early (E14) and late (E18) developmental stages of rat striatal NPCs in vitro. NPCs were isolated from E14 and E18 embryos and cultured for 7 days with or without Cr [5 mM]. Chronic treatment significantly increased the percentage of GABA-immunoreactive neurons as compared to untreated controls, both in the E14 (170.4 ± 4.7 %) and the E18 groups (129.3 ± 9.3 %). This effect was greater in E14 cultures (p < 0.05). Similarly, short-term treatment for 24 h resulted in increased induction (p < 0.05) of the GABA-ergic phenotype in E14 (163.0 ± 10.4 %), compared to E18 cultures (133.3 ± 9.5 %). Total neuronal cell numbers and general viability were not affected by Cr (p > 0.05). Protective effects of Cr against a metabolic insult were equal in E14 and E18 NPCs (p > 0.05). Cr exposure promoted morphological differentiation of GABA-ergic neurons, including neurite length in both groups (p < 0.05), but the number of branching points was increased only in the E18 group (p < 0.05). Our results demonstrate that the role of Cr as a GABA-ergic differentiation factor depends on the developmental stage of striatal NPCs, while Cr-mediated neuroprotection is not significantly influenced. These findings have potential implications for optimizing future cell replacement strategies in HD.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > NeuroCenter
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurosurgery
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Veterinary Pharmacology and Toxicology
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Neurochirurgie

UniBE Contributor:

Ducray, Angélique; Andereggen, Lukas and Widmer, Hans Rudolf

Subjects:

600 Technology > 630 Agriculture
500 Science
500 Science > 570 Life sciences; biology

ISSN:

0939-4451

Publisher:

Springer

Language:

English

Submitter:

Angélique Ducray

Date Deposited:

15 Sep 2016 13:59

Last Modified:

11 Sep 2017 18:06

Publisher DOI:

10.1007/s00726-016-2238-8

PubMed ID:

27129463

BORIS DOI:

10.7892/boris.87712

URI:

https://boris.unibe.ch/id/eprint/87712

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