Cargando…

Involvement of Antioxidant and Prevention of Mitochondrial Dysfunction, Anti-Neuroinflammatory Effect and Anti-Apoptotic Effect: Betaine Ameliorates Haloperidol-Induced Orofacial Dyskinesia in Rats

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Tseng, Hsiang-Chien, Wang, Mao-Hsien, Fang, Chih-Hsiang, Lin, Yi-Wen, Soung, Hung-Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377434/
https://www.ncbi.nlm.nih.gov/pubmed/37508996
http://dx.doi.org/10.3390/brainsci13071064
_version_ 1785079516805201920
author Tseng, Hsiang-Chien
Wang, Mao-Hsien
Fang, Chih-Hsiang
Lin, Yi-Wen
Soung, Hung-Sheng
author_facet Tseng, Hsiang-Chien
Wang, Mao-Hsien
Fang, Chih-Hsiang
Lin, Yi-Wen
Soung, Hung-Sheng
author_sort Tseng, Hsiang-Chien
collection PubMed
description 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.
format Online
Article
Text
id pubmed-10377434
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-103774342023-07-29 Involvement of Antioxidant and Prevention of Mitochondrial Dysfunction, Anti-Neuroinflammatory Effect and Anti-Apoptotic Effect: Betaine Ameliorates Haloperidol-Induced Orofacial Dyskinesia in Rats Tseng, Hsiang-Chien Wang, Mao-Hsien Fang, Chih-Hsiang Lin, Yi-Wen Soung, Hung-Sheng Brain Sci Article 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. MDPI 2023-07-12 /pmc/articles/PMC10377434/ /pubmed/37508996 http://dx.doi.org/10.3390/brainsci13071064 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tseng, Hsiang-Chien
Wang, Mao-Hsien
Fang, Chih-Hsiang
Lin, Yi-Wen
Soung, Hung-Sheng
Involvement of Antioxidant and Prevention of Mitochondrial Dysfunction, Anti-Neuroinflammatory Effect and Anti-Apoptotic Effect: Betaine Ameliorates Haloperidol-Induced Orofacial Dyskinesia in Rats
title Involvement of Antioxidant and Prevention of Mitochondrial Dysfunction, Anti-Neuroinflammatory Effect and Anti-Apoptotic Effect: Betaine Ameliorates Haloperidol-Induced Orofacial Dyskinesia in Rats
title_full Involvement of Antioxidant and Prevention of Mitochondrial Dysfunction, Anti-Neuroinflammatory Effect and Anti-Apoptotic Effect: Betaine Ameliorates Haloperidol-Induced Orofacial Dyskinesia in Rats
title_fullStr Involvement of Antioxidant and Prevention of Mitochondrial Dysfunction, Anti-Neuroinflammatory Effect and Anti-Apoptotic Effect: Betaine Ameliorates Haloperidol-Induced Orofacial Dyskinesia in Rats
title_full_unstemmed Involvement of Antioxidant and Prevention of Mitochondrial Dysfunction, Anti-Neuroinflammatory Effect and Anti-Apoptotic Effect: Betaine Ameliorates Haloperidol-Induced Orofacial Dyskinesia in Rats
title_short Involvement of Antioxidant and Prevention of Mitochondrial Dysfunction, Anti-Neuroinflammatory Effect and Anti-Apoptotic Effect: Betaine Ameliorates Haloperidol-Induced Orofacial Dyskinesia in Rats
title_sort involvement of antioxidant and prevention of mitochondrial dysfunction, anti-neuroinflammatory effect and anti-apoptotic effect: betaine ameliorates haloperidol-induced orofacial dyskinesia in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377434/
https://www.ncbi.nlm.nih.gov/pubmed/37508996
http://dx.doi.org/10.3390/brainsci13071064
work_keys_str_mv AT tsenghsiangchien involvementofantioxidantandpreventionofmitochondrialdysfunctionantineuroinflammatoryeffectandantiapoptoticeffectbetaineameliorateshaloperidolinducedorofacialdyskinesiainrats
AT wangmaohsien involvementofantioxidantandpreventionofmitochondrialdysfunctionantineuroinflammatoryeffectandantiapoptoticeffectbetaineameliorateshaloperidolinducedorofacialdyskinesiainrats
AT fangchihhsiang involvementofantioxidantandpreventionofmitochondrialdysfunctionantineuroinflammatoryeffectandantiapoptoticeffectbetaineameliorateshaloperidolinducedorofacialdyskinesiainrats
AT linyiwen involvementofantioxidantandpreventionofmitochondrialdysfunctionantineuroinflammatoryeffectandantiapoptoticeffectbetaineameliorateshaloperidolinducedorofacialdyskinesiainrats
AT sounghungsheng involvementofantioxidantandpreventionofmitochondrialdysfunctionantineuroinflammatoryeffectandantiapoptoticeffectbetaineameliorateshaloperidolinducedorofacialdyskinesiainrats