Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters

Background: Transcranial direct current stimulation (tDCS) is a technique that modulates neuronal activity and has been proposed as a potential therapeutic tool for attention-deficit/hyperactivity disorder (ADHD) symptoms. Although pilot studies have shown evidence of efficacy, its mechanism of acti...

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Main Authors: Douglas Teixeira Leffa, Bruna Bellaver, Artur Alban Salvi, Carla de Oliveira, Wolnei Caumo, Eugenio Horacio Grevet, Felipe Fregni, André Quincozes-Santos, Luis Augusto Rohde, Iraci L.S. Torres
Format: Article
Language:English
Published: Elsevier 2018-07-01
Series:Brain Stimulation
Subjects:
SHR
Online Access:http://www.sciencedirect.com/science/article/pii/S1935861X18301025
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author Douglas Teixeira Leffa
Bruna Bellaver
Artur Alban Salvi
Carla de Oliveira
Wolnei Caumo
Eugenio Horacio Grevet
Felipe Fregni
André Quincozes-Santos
Luis Augusto Rohde
Iraci L.S. Torres
spellingShingle Douglas Teixeira Leffa
Bruna Bellaver
Artur Alban Salvi
Carla de Oliveira
Wolnei Caumo
Eugenio Horacio Grevet
Felipe Fregni
André Quincozes-Santos
Luis Augusto Rohde
Iraci L.S. Torres
Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters
Brain Stimulation
ADHD
tDCS
SHR
author_facet Douglas Teixeira Leffa
Bruna Bellaver
Artur Alban Salvi
Carla de Oliveira
Wolnei Caumo
Eugenio Horacio Grevet
Felipe Fregni
André Quincozes-Santos
Luis Augusto Rohde
Iraci L.S. Torres
author_sort Douglas Teixeira Leffa
title Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters
title_short Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters
title_full Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters
title_fullStr Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters
title_full_unstemmed Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters
title_sort transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters
publisher Elsevier
series Brain Stimulation
issn 1935-861X
publishDate 2018-07-01
description Background: Transcranial direct current stimulation (tDCS) is a technique that modulates neuronal activity and has been proposed as a potential therapeutic tool for attention-deficit/hyperactivity disorder (ADHD) symptoms. Although pilot studies have shown evidence of efficacy, its mechanism of action remains unclear. Objective/Hypothesis: We evaluated the effects of tDCS on behavioral (working and long-term memory) and neurochemical (oxidative and inflammatory parameters) outcomes related to ADHD pathophysiology. We used the most widely accepted animal model of ADHD: spontaneously hypertensive rats (SHR). The selected behavioral outcomes have been shown to be altered in both ADHD patients and animal models, and were chosen for their relation to the proposed mechanistic action of tDCS. Methods: Adult male SHR and their control, the Wistar Kyoto rats (WKY), were subjected to 20 min of bicephalic tDCS or sham stimulation for 8 consecutive days. Working memory, long-term memory, and neurochemical outcomes were evaluated. Results: TDCS improved long-term memory deficits presented by the SHR. No change in working memory performance was observed. In the hippocampus, tDCS increased both the production of reactive oxygen species in SHR and the levels of the antioxidant molecule glutathione in both strains. TDCS also modulated inflammatory response in the brains of WKY by downregulating pro-inflammatory cytokines. Conclusion: TDCS had significant effects that were specific for strain, type of behavioral and neurochemical outcomes. The long-term memory improvement in the SHR may point to a possible therapeutic role of tDCS in ADHD that does not seem to be mediated by inflammatory markers. Additionally, the anti-inflammatory effects observed in the brain of WKY after tDCS needs to be further explored.
topic ADHD
tDCS
SHR
url http://www.sciencedirect.com/science/article/pii/S1935861X18301025
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spelling doaj-e29e955ae3a04311a999b2c81543f5f02021-03-19T07:11:58ZengElsevierBrain Stimulation1935-861X2018-07-01114743751Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parametersDouglas Teixeira Leffa0Bruna Bellaver1Artur Alban Salvi2Carla de Oliveira3Wolnei Caumo4Eugenio Horacio Grevet5Felipe Fregni6André Quincozes-Santos7Luis Augusto Rohde8Iraci L.S. Torres9Post-Graduate Program in Medicine: Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Animal Experimentation Unit and Graduate Research Group, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Laboratory of Pain Pharmacology and Neuromodulation: Pre Clinical Studies - Pharmacology Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, BrazilBiochemistry Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, BrazilAnimal Experimentation Unit and Graduate Research Group, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Laboratory of Pain Pharmacology and Neuromodulation: Pre Clinical Studies - Pharmacology Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, BrazilPost-Graduate Program in Medicine: Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Animal Experimentation Unit and Graduate Research Group, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Laboratory of Pain Pharmacology and Neuromodulation: Pre Clinical Studies - Pharmacology Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, BrazilPost-Graduate Program in Medicine: Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Pain and Palliative Care Service, Laboratory of Pain & Neuromodulation, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, BrazilPsychiatry Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; ADHD Outpatient Program, Hospital de Clínicas de Porto Alegre, BrazilLaboratory of Neuromodulation, Department of Physical Medicine & Rehabilitation, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard University, Boston, United StatesBiochemistry Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, BrazilPsychiatry Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; ADHD Outpatient Program, Hospital de Clínicas de Porto Alegre, Brazil; National Institute of Developmental Psychiatry for Children and Adolescents, BrazilPost-Graduate Program in Medicine: Medical Sciences, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Animal Experimentation Unit and Graduate Research Group, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Laboratory of Pain Pharmacology and Neuromodulation: Pre Clinical Studies - Pharmacology Department, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Corresponding author. Departamento de Farmacologia - ICBS, UFRGS; Rua Sarmento Leite, 500 sala 305, 90050-170, Porto Alegre, RS, Brazil.Background: Transcranial direct current stimulation (tDCS) is a technique that modulates neuronal activity and has been proposed as a potential therapeutic tool for attention-deficit/hyperactivity disorder (ADHD) symptoms. Although pilot studies have shown evidence of efficacy, its mechanism of action remains unclear. Objective/Hypothesis: We evaluated the effects of tDCS on behavioral (working and long-term memory) and neurochemical (oxidative and inflammatory parameters) outcomes related to ADHD pathophysiology. We used the most widely accepted animal model of ADHD: spontaneously hypertensive rats (SHR). The selected behavioral outcomes have been shown to be altered in both ADHD patients and animal models, and were chosen for their relation to the proposed mechanistic action of tDCS. Methods: Adult male SHR and their control, the Wistar Kyoto rats (WKY), were subjected to 20 min of bicephalic tDCS or sham stimulation for 8 consecutive days. Working memory, long-term memory, and neurochemical outcomes were evaluated. Results: TDCS improved long-term memory deficits presented by the SHR. No change in working memory performance was observed. In the hippocampus, tDCS increased both the production of reactive oxygen species in SHR and the levels of the antioxidant molecule glutathione in both strains. TDCS also modulated inflammatory response in the brains of WKY by downregulating pro-inflammatory cytokines. Conclusion: TDCS had significant effects that were specific for strain, type of behavioral and neurochemical outcomes. The long-term memory improvement in the SHR may point to a possible therapeutic role of tDCS in ADHD that does not seem to be mediated by inflammatory markers. Additionally, the anti-inflammatory effects observed in the brain of WKY after tDCS needs to be further explored.http://www.sciencedirect.com/science/article/pii/S1935861X18301025ADHDtDCSSHR