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 |
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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 |
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