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

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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.

Original languageEnglish
Pages (from-to)1079-1087
Number of pages9
JournalBrain Stimulation
Volume10
Issue number6
DOIs
Publication statusPublished - 2017 Nov 1

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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
N-Methyl-D-Aspartate Receptors
Diabetes Mellitus
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biophysics
  • Clinical Neurology

Cite this

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title = "Repeated transcranial direct current stimulation improves cognitive dysfunction and synaptic plasticity deficit in the prefrontal cortex of streptozotocin-induced diabetic rats",
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.",
author = "Yi-Jen Wu and Chou-Ching Lin and Yeh, {Che Ming} and Chien, {Miao Er} and Tsao, {Ming Chung} and Philip Tseng and Chin-Wei Huang and Kuei-Sen Hsu",
year = "2017",
month = "11",
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doi = "10.1016/j.brs.2017.08.007",
language = "English",
volume = "10",
pages = "1079--1087",
journal = "Brain Stimulation",
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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 - 2017/11/1

Y1 - 2017/11/1

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.

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