{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:51:16Z","timestamp":1792144276290,"version":"4.4.0"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["anatomypubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Anatomical Record"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Parkinson's disease (PD) is the most common age\u2010related neurodegenerative disease worldwide. S\u2010adenosyl methionine (SAMe), a methyl donor that plays an important role in DNA methylation, could replenish the cellular antioxidant glutathione (GSH). Herein, we investigated the neuroprotective effects of SAMe in 6\u2010hydroxydopamine (6\u2010OHDA) rat models of PD and elucidated the underlying mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>PD model rats were developed by injecting 6\u2010OHDA stereotaxically into the striatum. In Phase 1 of the study, we performed the neurobehavioral tests, GSH assay, and histopathology to evaluate the neuroprotective effects of SAMe. The animals were treated with SAMe (150 or 300\u2009mg\/kg body weight) orally for 28\u2009days. The positive control group received selegiline (5\u00a0mg\/kg), whereas the disease control group received normal saline.<\/jats:p><jats:p>In Phase 2, we evaluated the striatal dopamine levels and performed DNA methylation assay to uncover the mechanism of action of SAMe. In this phase, a higher dose of SAMe (300\u2009mg\/kg) was used.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SAMe (300\u2009mg\/kg) treatment for 4\u2009weeks significantly attenuated the abnormal circling behavior in PD rats (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Moreover, SAMe at both doses (150 and 300\u2009mg\/kg) enhanced the performance of PD rats in the open field test and stepping test (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). SAMe treatment significantly increased the GSH levels, and at high dose, SAMe restricted neuronal loss in the striatum of PD\u2010model rats (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Moreover, SAMe treatment led to a significant recovery in the dopamine levels and improved the DNA methylation status in the dopaminergic neurons (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) of PD model rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>SAMe exhibits antioxidant activity and DNA methylation modulating effects in 6\u2010OHDA model PD rats. Moreover, SAMe prevents neuronal loss in PD rats suggesting that SAMe has therapeutic potential in preventing PD development. The neuroprotective potential of SAMe is greater at high doses.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ar.24948","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T09:34:35Z","timestamp":1651052075000},"page":"820-830","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["S\u2010adenosyl methionine improves motor co\u2010ordination with reduced oxidative stress, dopaminergic neuronal loss, and <scp>DNA<\/scp> methylation in the brain striatum of 6\u2010hydroxydopamine\u2010induced neurodegeneration in rats"],"prefix":"10.1002","volume":"306","author":[{"given":"Sharmila","family":"Jalgaonkar","sequence":"first","affiliation":[{"name":"Department of Pharmacology &amp; Therapeutics Seth G. S. Medical College and King Edward Memorial Hospital  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snehalata","family":"Gajbhiye","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Therapeutics Seth G. S. Medical College and King Edward Memorial Hospital  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohsin","family":"Sayyed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Therapeutics Seth G. S. Medical College and King Edward Memorial Hospital  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6467-1378","authenticated-orcid":false,"given":"Raakhi","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Therapeutics Seth G. S. Medical College and King Edward Memorial Hospital  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishtha","family":"Khatri","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Therapeutics Seth G. S. Medical College and King Edward Memorial Hospital  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urwashi","family":"Parmar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Therapeutics Seth G. S. Medical College and King Edward Memorial Hospital  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Shankar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Therapeutics Seth G. S. Medical College and King Edward Memorial Hospital  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/942981"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2014.00397"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702589"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.15344\/2456-8171\/2016\/109"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159x13666151030102718"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30295-3"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/15592294.2019.1588682"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.18203\/2319-2003.ijbcp"},{"issue":"3","key":"e_1_2_11_10_1","first-page":"137","article-title":"Oxidative stress\u2010related biomarkers in Parkinson's disease: A systematic review and meta\u2010analysis","volume":"17","author":"Khan Z.","year":"2018","journal-title":"Iranian Journal of Neurology"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.2217\/epi.10.43"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170177"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.11855\/j.issn.0577-7402"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1109\/ICCME.2007.4381977"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21062220"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/9409363"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/76\/5.1158S"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-05-03863.1995"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00056.2014"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389202914666131210210559"},{"issue":"2","key":"e_1_2_11_21_1","first-page":"257","article-title":"Histological alterations following 6\u2010hydroxydopamin\u2010induced parkinson model","volume":"15","author":"Samah L.","year":"2013","journal-title":"Mansoura Veterinary Medical Journal"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.29.1_supplement.134.3"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.4103\/0253-7613.103275"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24081583"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.8277"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-017-1392-1"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0167201"},{"issue":"1","key":"e_1_2_11_28_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1139\/jpn.0507","article-title":"The effect of methionine and S\u2010adenosylmethionine on S\u2010adenosylmethionine levels in the rat brain","volume":"30","author":"Young S. 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