{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T16:28:36Z","timestamp":1786552116762,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,12]],"date-time":"2023-07-12T00:00:00Z","timestamp":1689120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Yuan-Shan Branch of Taipei Veteran General Hospital","award":["YSVH10902"],"award-info":[{"award-number":["YSVH10902"]}]},{"name":"Yuan-Shan Branch of Taipei Veteran General Hospital","award":["2019SKHADR031"],"award-info":[{"award-number":["2019SKHADR031"]}]},{"name":"Shin Kong Wu Ho-Su Memorial Hospital","award":["YSVH10902"],"award-info":[{"award-number":["YSVH10902"]}]},{"name":"Shin Kong Wu Ho-Su Memorial Hospital","award":["2019SKHADR031"],"award-info":[{"award-number":["2019SKHADR031"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>With its pathophysiological characteristics strongly similar to patients with tardive dyskinesia (TD), haloperidol (HP)-induced neurotoxicity and orofacial dyskinesia (OD) in animal models have long been used to study human TD. This study aimed to explore the potential protective effects of betaine (BT), a vital biochemical compound present in plants, microorganisms, animals, and various dietary sources. The study focused on investigating the impact of BT on haloperidol (HP)-induced orofacial dyskinesia (OD) in rats, as well as the underlying neuroprotective mechanisms. To induce the development of OD, which is characterized by increased vacuous chewing movement (VCM) and tongue protrusion (TP), rats were administered HP (1 mg\/kg i.p.) for 21 consecutive days. BT was administered intraperitoneally (i.p.) at doses of 30 and 100 mg\/kg, 60 min later, for 21 successive days. On the 21st day, after evaluating OD behavior, the rats were sacrificed, and various measurements were taken to assess the nitrosative and oxidative status, antioxidant capacity, mitochondrial function, neuroinflammation, and apoptotic markers in the striatum. The results demonstrated that (1) HP induced OD development, and (2) BT was found to prevent most of the HP-induced OD; decrease oxidative stress levels; increase anti-oxidation power; prevent mitochondrial dysfunction; and reduce the levels of neuroinflammatory and apoptotic markers in the striatum. Our results demonstrate that the neuroprotective effects of BT against HP-induced OD are credited to its antioxidant prevention of mitochondrial dysfunction, anti-neuroinflammatory effects, and anti-apoptotic effects, suggesting that BT may be a novel therapeutic candidate in delaying or treating human TD in clinical settings. However, further studies will be warranted to extrapolate preclinical findings into clinical studies for a better understanding of the role of BT.<\/jats:p>","DOI":"10.3390\/brainsci13071064","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T01:43:22Z","timestamp":1689212602000},"page":"1064","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Involvement of Antioxidant and Prevention of Mitochondrial Dysfunction, Anti-Neuroinflammatory Effect and Anti-Apoptotic Effect: Betaine Ameliorates Haloperidol-Induced Orofacial Dyskinesia in Rats"],"prefix":"10.3390","volume":"13","author":[{"given":"Hsiang-Chien","family":"Tseng","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, Taiwan"},{"name":"School of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao-Hsien","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, En Chu Kon Hospital, Sanshia District, New Taipei City 23702, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7797-6584","authenticated-orcid":false,"given":"Chih-Hsiang","family":"Fang","sequence":"additional","affiliation":[{"name":"China Medical University Hospital, Taichung 404332, Taiwan"},{"name":"Trauma and Emergency Center, China Medical University Hospital, Taichung 404018, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Wen","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Sheng","family":"Soung","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yuan-Shan Branch of Taipei Veteran General Hospital, Yilan 26604, Taiwan"},{"name":"Department of Biomedical Engineering, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,12]]},"reference":[{"key":"ref_1","unstructured":"Vasan, S., and Padhy, R.K. 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