Creatine and neurotrophin-4/5 promote survival of nitric oxide synthase-expressing interneurons in striatal cultures

Autor: Angélique Ducray, Hans Rudolf Widmer, Stefan Kipfer, Alexander W. Huber, Theo Wallimann, Uwe Schlattner, Robert H. Andres, Rolf W. Seiler
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: 2006
Předmět:
medicine.medical_specialty
Ganglionic eminence
Interneuron
MESH: Rats
Cell Survival
MESH: Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type I
Biology
Creatine
Nitric oxide
MESH: Corpus Striatum
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Interneurons
Internal medicine
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology

medicine
Animals
MESH: Animals
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology

Nerve Growth Factors
Rats
Wistar

Cells
Cultured

030304 developmental biology
MESH: Drug Combinations
0303 health sciences
MESH: Creatine
MESH: Nerve Growth Factors
General Neuroscience
MESH: Rats
Wistar

MESH: Interneurons
Corpus Striatum
Rats
3. Good health
Nitric oxide synthase
Drug Combinations
Phosphagen
Endocrinology
medicine.anatomical_structure
chemistry
nervous system
MESH: Cell Survival
biology.protein
GABAergic
030217 neurology & neurosurgery
Neurotrophin
MESH: Cells
Cultured
Zdroj: Neuroscience Letters
Neuroscience Letters, Elsevier, 2006, 395 (1), pp.57-62. ⟨10.1016/j.neulet.2005.10.051⟩
ISSN: 0304-3940
DOI: 10.1016/j.neulet.2005.10.051⟩
Popis: International audience; Nitric oxide (NO) mediates a variety of physiological functions in the central nervous system and acts as an important developmental regulator. Striatal interneurons expressing neuronal nitric oxide synthase (nNOS) have been described to be relatively spared from the progressive cell loss in Huntington's disease (HD). We have recently shown that creatine, which supports the phosphagen energy system, induces the differentiation of GABAergic cells in cultured striatal tissue. Moreover, neurotrophin-4/5 (NT-4/5) has been found to promote the survival and differentiation of cultured striatal neurons. In the present study, we assessed the effects of creatine and NT-4/5 on nNOS-immunoreactive (-ir) neurons of E14 rat ganglionic eminences grown for 1 week in culture. Chronic administration of creatine [5mM], NT-4/5 [10ng/ml], or a combination of both factors significantly increased numbers of nNOS-ir neurons. NT-4/5 exposure also robustly increased levels of nNOS protein. Interestingly, only NT-4/5 and combined treatment significantly increased general viability but no effects were seen for creatine supplementation alone. In addition, NT-4/5 and combined treatment resulted in a significant larger soma size and number of primary neurites of nNOS-ir neurons while creatine administration alone exerted no effects. Double-immunolabeling studies revealed that all nNOS-ir cells co-localized with GABA. In summary, our findings suggest that creatine and NT-4/5 affect differentiation and/or survival of striatal nNOS-ir GABAergic interneurons. These findings provide novel insights into the biology of developing striatal neurons and highlight the potential of both creatine and NT-4/5 as therapeutics for HD.
Databáze: OpenAIRE