Therapeutic effects of anodal transcranial direct current stimulation in a rat model of ADHD

  1. Da Hee Jung
  2. Sung Min Ahn
  3. Malk Eun Pak
  4. Hong Ju Lee
  5. Young Jin Jung
  6. Kibong Kim
  7. Yong-Il Shin
  8. Hwa Kyoung Shin
  9. Byung Tae Choi  Is a corresponding author
  1. Pusan National University, Republic of Korea
  2. Dongseo University, Republic of Korea

Abstract

Most therapeutic candidates for treating attention deficit hyperactivity disorder (ADHD) have focused on modulating the dopaminergic neurotransmission system with neurotrophic factors. Regulation of this system by transcranial direct current stimulation (tDCS) could contribute to the recovery of cognitive symptoms observed in patients with ADHD. Here, male spontaneously hypertensive (SHR) rats were subjected to consecutive high-definition tDCS (HD-tDCS) (20 min, 50 μA, current density 63.7 A/m2, charge density 76.4 kC/m2) over the prefrontal cortex. This treatment alleviated cognitive deficits, with an increase in tyrosine hydroxylase and vesicular monoamine transporter 2 and significantly decreased plasma membrane reuptake transporter (DAT). HD-tDCS application increased the expression of several neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF), and activated hippocampal neurogenesis. Our results suggest that anodal HD-tDCS over the prefrontal cortex may ameliorate cognitive dysfunction via regulation of DAT and BDNF in the mesocorticolimbic dopaminergic pathways, and therefore represents a potential adjuvant therapy for ADHD.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures and Tables

Article and author information

Author details

  1. Da Hee Jung

    Department of Korean Medical Science, Pusan National University, Yangsan, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  2. Sung Min Ahn

    Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  3. Malk Eun Pak

    Korean Medical Science Research Center for Healthy-Aging, Pusan National University, Yangsan, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  4. Hong Ju Lee

    Department of Korean Medical Science, Pusan National University, Yangsan, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  5. Young Jin Jung

    Department of Radiological Science, Dongseo University, Busan, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  6. Kibong Kim

    Department of Korean Pediatrics, Pusan National University, Yangsan, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5724-4653
  7. Yong-Il Shin

    Department of Rehabilitation Medicine, Pusan National University, Yangsan, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  8. Hwa Kyoung Shin

    Department of Korean Medical Science, Pusan National University, Yangsan, Republic of Korea
    Competing interests
    The authors declare that no competing interests exist.
  9. Byung Tae Choi

    Department of Korean Medical Science, Pusan National University, Yangsan, Republic of Korea
    For correspondence
    choibt@pusan.ac.kr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5965-4346

Funding

National Research Foundation of Korea (2018R1A2A2A05018926)

  • Byung Tae Choi

National Research Foundation of Korea (2014R1A5A2009936)

  • Byung Tae Choi

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experiments were approved by the Pusan National University Animal Care and Use Committee and were performed in accordance with the National Institutes of Health Guidelines (PNU-2018-1932)

Copyright

© 2020, Jung et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,891
    views
  • 285
    downloads
  • 17
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Da Hee Jung
  2. Sung Min Ahn
  3. Malk Eun Pak
  4. Hong Ju Lee
  5. Young Jin Jung
  6. Kibong Kim
  7. Yong-Il Shin
  8. Hwa Kyoung Shin
  9. Byung Tae Choi
(2020)
Therapeutic effects of anodal transcranial direct current stimulation in a rat model of ADHD
eLife 9:e56359.
https://doi.org/10.7554/eLife.56359

Share this article

https://doi.org/10.7554/eLife.56359

Further reading

    1. Neuroscience
    Charles R Heller, Gregory R Hamersky, Stephen V David
    Research Article

    Categorical sensory representations are critical for many behaviors, including speech perception. In the auditory system, categorical information is thought to arise hierarchically, becoming increasingly prominent in higher-order cortical regions. The neural mechanisms that support this robust and flexible computation remain poorly understood. Here, we studied sound representations in the ferret primary and non-primary auditory cortex while animals engaged in a challenging sound discrimination task. Population-level decoding of simultaneously recorded single neurons revealed that task engagement caused categorical sound representations to emerge in non-primary auditory cortex. In primary auditory cortex, task engagement caused a general enhancement of sound decoding that was not specific to task-relevant categories. These findings are consistent with mixed selectivity models of neural disentanglement, in which early sensory regions build an overcomplete representation of the world and allow neurons in downstream brain regions to flexibly and selectively read out behaviorally relevant, categorical information.

    1. Neuroscience
    2. Stem Cells and Regenerative Medicine
    Amber R Philp, Carolina R Reyes ... Francisco J Rivera
    Short Report

    Revealing unknown cues that regulate oligodendrocyte progenitor cell (OPC) function in remyelination is important to optimise the development of regenerative therapies for multiple sclerosis (MS). Platelets are present in chronic non-remyelinated lesions of MS and an increase in circulating platelets has been described in experimental autoimmune encephalomyelitis (EAE) mice, an animal model for MS. However, the contribution of platelets to remyelination remains unexplored. Here we show platelet aggregation in proximity to OPCs in areas of experimental demyelination. Partial depletion of circulating platelets impaired OPC differentiation and remyelination, without altering blood-brain barrier stability and neuroinflammation. Transient exposure to platelets enhanced OPC differentiation in vitro, whereas sustained exposure suppressed this effect. In a mouse model of thrombocytosis (Calr+/-), there was a sustained increase in platelet aggregation together with a reduction of newly-generated oligodendrocytes following toxin-induced demyelination. These findings reveal a complex bimodal contribution of platelet to remyelination and provide insights into remyelination failure in MS.