{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T01:27:25Z","timestamp":1777858045225,"version":"3.51.4"},"reference-count":49,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2010,12,17]],"date-time":"2010-12-17T00:00:00Z","timestamp":1292544000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:p>DNA methylation is coupled with one-carbon metabolism involving homocysteine\/methionine interconversion. Correlation between plasma homocysteine levels and leukocyte global DNA methylation was reported but not always replicated. Nicotinamide N-methyltransferase (NNMT) is a determinant of plasma homocysteine levels. Findings suggest alteration of one-carbon metabolism in schizophrenia etiology; hyperhomocysteinemia was observed in schizophrenia. A recent study carried out by the authors of this paper found an association between NNMT and schizophrenia and decreased post-mortem brain NNMT mRNA levels. The present study assessed the interrelationship between brain and leukocytes global DNA methylation and plasma homocysteine levels, and between hyperhomocysteinemia and brain NNMT expression.<\/jats:p>\n                  <jats:p>Mice were administered homocysteine in drinking water. Percentage global genome DNA methylation was measured using the cytosine-extension method, and NNMT expression was measured using real-time quantitative reverse transcriptase PCR (qRT-PCR). Homocysteine administration resulted in a 10-fold increase in plasma homocysteine. However, there was no change in global DNA methylation in lymphocytes or in the frontal cortex. No significant intra-individual correlation was found between global DNA methylation in leukocytes and frontal cortex, suggesting that leukocyte global DNA methylation may not serve as a marker for brain global DNA methylation. No difference was found in NNMT expression in homocysteine-treated mice compared with control mice.<\/jats:p>\n                  <jats:p>In conclusion, relatively short-term hyperhomocysteinemia in mice does not reproduce or lead to alterations reported in one-carbon metabolism in disorders associated with lifelong elevated plasma homocysteine.<\/jats:p>","DOI":"10.1177\/0269881110388328","type":"journal-article","created":{"date-parts":[[2010,12,17]],"date-time":"2010-12-17T22:35:40Z","timestamp":1292625340000},"page":"976-981","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Hyperhomocysteinemia does not affect global DNA methylation and nicotinamide\n                    <i>N<\/i>\n                    -methyltransferase expression in mice"],"prefix":"10.1177","volume":"25","author":[{"given":"Anna","family":"Bromberg","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel."},{"name":"Psychiatry Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel."},{"name":"Mental Health Center and Division of Psychiatry, Ben-Gurion University of the Negev, Beer-Sheva, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Levine","sequence":"additional","affiliation":[{"name":"Mental Health Center and Division of Psychiatry, Ben-Gurion University of the Negev, Beer-Sheva, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"RH","family":"Belmaker","sequence":"additional","affiliation":[{"name":"Psychiatry Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel."},{"name":"Mental Health Center and Division of Psychiatry, Ben-Gurion University of the Negev, Beer-Sheva, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galila","family":"Agam","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel."},{"name":"Psychiatry Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel."},{"name":"Mental Health Center and Division of Psychiatry, Ben-Gurion University of the Negev, Beer-Sheva, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2010,12,17]]},"reference":[{"key":"bibr1-0269881110388328","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2006.03.006"},{"key":"bibr2-0269881110388328","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2004.01.003"},{"key":"bibr3-0269881110388328","doi-asserted-by":"publisher","DOI":"10.1016\/0378-4347(87)80438-3"},{"key":"bibr4-0269881110388328","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-004-0232-x"},{"key":"bibr5-0269881110388328","unstructured":"Bromberg A, Lerer E, Belmaker R, Ebstein RP and Agam G (submitted) Nicotinamide N-methyltransferase (NNMT) gene in schizophrenia: association in family-based study and decreased expression in post mortem frontal 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