{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:37:18Z","timestamp":1760236638384,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T00:00:00Z","timestamp":1639180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Gda\u0144sk Medical University","award":["ST-57 02-0057\/07\/248"],"award-info":[{"award-number":["ST-57 02-0057\/07\/248"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Brain pathologies evoked by thiamine deficiency can be aggravated by mild zinc excess. Cholinergic neurons are the most susceptible to such cytotoxic signals. Sub-toxic zinc excess aggravates the injury of neuronal SN56 cholinergic cells under mild thiamine deficiency. The excessive cell loss is caused by Zn interference with acetyl-CoA metabolism. The aim of this work was to investigate whether and how astroglial C6 cells alleviated the neurotoxicity of Zn to cultured SN56 cells in thiamine-deficient media. Low Zn concentrations did not affect astroglial C6 and primary glial cell viability in thiamine-deficient conditions. Additionally, parameters of energy metabolism were not significantly changed. Amprolium (a competitive inhibitor of thiamine uptake) augmented thiamine pyrophosphate deficits in cells, while co-treatment with Zn enhanced the toxic effect on acetyl-CoA metabolism. SN56 cholinergic neuronal cells were more susceptible to these combined insults than C6 and primary glial cells, which affected pyruvate dehydrogenase activity and the acetyl-CoA level. A co-culture of SN56 neurons with astroglial cells in thiamine-deficient medium eliminated Zn-evoked neuronal loss. These data indicate that astroglial cells protect neurons against Zn and thiamine deficiency neurotoxicity by preserving the acetyl-CoA level.<\/jats:p>","DOI":"10.3390\/ijms222413337","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T01:28:11Z","timestamp":1639358891000},"page":"13337","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Protection of Cholinergic Neurons against Zinc Toxicity by Glial Cells in Thiamine-Deficient Media"],"prefix":"10.3390","volume":"22","author":[{"given":"Sylwia","family":"Gul-Hinc","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Michno","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marlena","family":"Zy\u015bk","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2753-2763","authenticated-orcid":false,"given":"Andrzej","family":"Szutowicz","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Jankowska-Kulawy","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5715-1211","authenticated-orcid":false,"given":"Anna","family":"Ronowska","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.nut.2010.07.021","article-title":"Brain fuel metabolism, aging, and Alzheimer\u2019s disease","volume":"27","author":"Cunnane","year":"2011","journal-title":"Nutrition"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1007\/s11064-013-1060-x","article-title":"Acetyl-CoA the key factor for survival or death of cholinergic neurons in course of neurodegenerative diseases","volume":"38","author":"Szutowicz","year":"2013","journal-title":"Neurochem. 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