Repeated transcranial direct current stimulation improves cognitive dysfunction and synaptic plasticity deficit in the prefrontal cortex of streptozotocin-induced diabetic rats

Yi Jen Wu, Chou Ching Lin, Che Ming Yeh, Miao Er Chien, Ming Chung Tsao, Philip Tseng, Chin Wei Huang, Kuei Sen Hsu

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Cognitive dysfunction is commonly observed in diabetic patients. We have previously reported that anodal transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex can facilitate visuospatial working memory in diabetic patients with concomitant diabetic peripheral neuropathy and mild cognitive impairment, but the underlying mechanisms remain unclear. Objective: We investigated the cellular mechanisms underlying the effect of tDCS on cognitive decline in streptozotocin (STZ)-induced diabetic rats. Methods: STZ-induced diabetic rats were subjected to either repeated anodal tDCS or sham stimulation over the medial prefrontal cortex (mPFC). Spatial working memory performance in delayed nonmatch-to-place T maze task (DNMT), the induction of long-term potentiation (LTP) in the mPFC, and dendritic morphology of Golgi-stained pyramidal neurons in the mPFC were assessed. Results: Repeated applications of prefrontal anodal tDCS improved spatial working memory performance in DNMT and restored the impaired mPFC LTP of diabetic rats. The mPFC of tDCS-treated diabetic rats exhibited higher levels of brain-derived neurotrophic factor (BDNF) protein and N-Methyl-d-aspartate receptor (NMDAR) subunit mRNA and protein compared to sham stimulation group. Furthermore, anodal tDCS significantly increased dendritic spine density on the apical dendrites of mPFC layer V pyramidal cells in diabetic rats, whereas the complexity of basal and apical dendritic trees was unaltered. Conclusions: Our findings suggest that repeated anodal tDCS may improve spatial working memory performance in streptozotocin-induced diabetic rats through augmentation of synaptic plasticity that requires BDNF secretion and transcription/translation of NMDARs in the mPFC, and support the therapeutic potential of tDCS for cognitive decline in diabetes mellitus patients.

Original languageEnglish
JournalBrain Stimulation
DOIs
Publication statusAccepted/In press - 2017

Fingerprint

Neuronal Plasticity
Streptozocin
Prefrontal Cortex
Short-Term Memory
Long-Term Potentiation
Pyramidal Cells
Brain-Derived Neurotrophic Factor
Dendritic Spines
Cognitive Dysfunction
Transcranial Direct Current Stimulation
Diabetic Neuropathies
Protein Subunits
Nerve Growth Factors
Peripheral Nervous System Diseases
Dendrites
Diabetes Mellitus
Messenger RNA

Keywords

  • Brain-derived neurotrophic factor
  • Cognitive function
  • Diabetes mellitus
  • Medial prefrontal cortex
  • N-Methyl-d-aspartate receptor
  • Transcranial direct current stimulation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biophysics
  • Clinical Neurology

Cite this

Repeated transcranial direct current stimulation improves cognitive dysfunction and synaptic plasticity deficit in the prefrontal cortex of streptozotocin-induced diabetic rats. / Wu, Yi Jen; Lin, Chou Ching; Yeh, Che Ming; Chien, Miao Er; Tsao, Ming Chung; Tseng, Philip; Huang, Chin Wei; Hsu, Kuei Sen.

In: Brain Stimulation, 2017.

Research output: Contribution to journalArticle

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abstract = "Background: Cognitive dysfunction is commonly observed in diabetic patients. We have previously reported that anodal transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex can facilitate visuospatial working memory in diabetic patients with concomitant diabetic peripheral neuropathy and mild cognitive impairment, but the underlying mechanisms remain unclear. Objective: We investigated the cellular mechanisms underlying the effect of tDCS on cognitive decline in streptozotocin (STZ)-induced diabetic rats. Methods: STZ-induced diabetic rats were subjected to either repeated anodal tDCS or sham stimulation over the medial prefrontal cortex (mPFC). Spatial working memory performance in delayed nonmatch-to-place T maze task (DNMT), the induction of long-term potentiation (LTP) in the mPFC, and dendritic morphology of Golgi-stained pyramidal neurons in the mPFC were assessed. Results: Repeated applications of prefrontal anodal tDCS improved spatial working memory performance in DNMT and restored the impaired mPFC LTP of diabetic rats. The mPFC of tDCS-treated diabetic rats exhibited higher levels of brain-derived neurotrophic factor (BDNF) protein and N-Methyl-d-aspartate receptor (NMDAR) subunit mRNA and protein compared to sham stimulation group. Furthermore, anodal tDCS significantly increased dendritic spine density on the apical dendrites of mPFC layer V pyramidal cells in diabetic rats, whereas the complexity of basal and apical dendritic trees was unaltered. Conclusions: Our findings suggest that repeated anodal tDCS may improve spatial working memory performance in streptozotocin-induced diabetic rats through augmentation of synaptic plasticity that requires BDNF secretion and transcription/translation of NMDARs in the mPFC, and support the therapeutic potential of tDCS for cognitive decline in diabetes mellitus patients.",
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author = "Wu, {Yi Jen} and Lin, {Chou Ching} and Yeh, {Che Ming} and Chien, {Miao Er} and Tsao, {Ming Chung} and Philip Tseng and Huang, {Chin Wei} and Hsu, {Kuei Sen}",
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T1 - Repeated transcranial direct current stimulation improves cognitive dysfunction and synaptic plasticity deficit in the prefrontal cortex of streptozotocin-induced diabetic rats

AU - Wu, Yi Jen

AU - Lin, Chou Ching

AU - Yeh, Che Ming

AU - Chien, Miao Er

AU - Tsao, Ming Chung

AU - Tseng, Philip

AU - Huang, Chin Wei

AU - Hsu, Kuei Sen

PY - 2017

Y1 - 2017

N2 - Background: Cognitive dysfunction is commonly observed in diabetic patients. We have previously reported that anodal transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex can facilitate visuospatial working memory in diabetic patients with concomitant diabetic peripheral neuropathy and mild cognitive impairment, but the underlying mechanisms remain unclear. Objective: We investigated the cellular mechanisms underlying the effect of tDCS on cognitive decline in streptozotocin (STZ)-induced diabetic rats. Methods: STZ-induced diabetic rats were subjected to either repeated anodal tDCS or sham stimulation over the medial prefrontal cortex (mPFC). Spatial working memory performance in delayed nonmatch-to-place T maze task (DNMT), the induction of long-term potentiation (LTP) in the mPFC, and dendritic morphology of Golgi-stained pyramidal neurons in the mPFC were assessed. Results: Repeated applications of prefrontal anodal tDCS improved spatial working memory performance in DNMT and restored the impaired mPFC LTP of diabetic rats. The mPFC of tDCS-treated diabetic rats exhibited higher levels of brain-derived neurotrophic factor (BDNF) protein and N-Methyl-d-aspartate receptor (NMDAR) subunit mRNA and protein compared to sham stimulation group. Furthermore, anodal tDCS significantly increased dendritic spine density on the apical dendrites of mPFC layer V pyramidal cells in diabetic rats, whereas the complexity of basal and apical dendritic trees was unaltered. Conclusions: Our findings suggest that repeated anodal tDCS may improve spatial working memory performance in streptozotocin-induced diabetic rats through augmentation of synaptic plasticity that requires BDNF secretion and transcription/translation of NMDARs in the mPFC, and support the therapeutic potential of tDCS for cognitive decline in diabetes mellitus patients.

AB - Background: Cognitive dysfunction is commonly observed in diabetic patients. We have previously reported that anodal transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex can facilitate visuospatial working memory in diabetic patients with concomitant diabetic peripheral neuropathy and mild cognitive impairment, but the underlying mechanisms remain unclear. Objective: We investigated the cellular mechanisms underlying the effect of tDCS on cognitive decline in streptozotocin (STZ)-induced diabetic rats. Methods: STZ-induced diabetic rats were subjected to either repeated anodal tDCS or sham stimulation over the medial prefrontal cortex (mPFC). Spatial working memory performance in delayed nonmatch-to-place T maze task (DNMT), the induction of long-term potentiation (LTP) in the mPFC, and dendritic morphology of Golgi-stained pyramidal neurons in the mPFC were assessed. Results: Repeated applications of prefrontal anodal tDCS improved spatial working memory performance in DNMT and restored the impaired mPFC LTP of diabetic rats. The mPFC of tDCS-treated diabetic rats exhibited higher levels of brain-derived neurotrophic factor (BDNF) protein and N-Methyl-d-aspartate receptor (NMDAR) subunit mRNA and protein compared to sham stimulation group. Furthermore, anodal tDCS significantly increased dendritic spine density on the apical dendrites of mPFC layer V pyramidal cells in diabetic rats, whereas the complexity of basal and apical dendritic trees was unaltered. Conclusions: Our findings suggest that repeated anodal tDCS may improve spatial working memory performance in streptozotocin-induced diabetic rats through augmentation of synaptic plasticity that requires BDNF secretion and transcription/translation of NMDARs in the mPFC, and support the therapeutic potential of tDCS for cognitive decline in diabetes mellitus patients.

KW - Brain-derived neurotrophic factor

KW - Cognitive function

KW - Diabetes mellitus

KW - Medial prefrontal cortex

KW - N-Methyl-d-aspartate receptor

KW - Transcranial direct current stimulation

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