Transcranial theta-burst stimulation alters GLT-1 and vGluT1 expression in rat cerebellar cortex

Mancic, Bojana; Stevanović, Ivana; Ilić, Tihomir V.; Djurić, Ana; Stojanović, Ivana; Milanović, Svetlana; Ninković, Milica

doi:10.1016/j.neuint.2016.09.009

Cited by 18 publications

(18 citation statements)

References 57 publications

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“…During the TBS, the rats were slightly stressed and immobilized manually. The coil was gently relied on the rats' head, centring the coil right above bregma [25].…”

Section: Tbs-induced Bdnf Expression In Eaementioning

confidence: 99%

Theta burst stimulation influence the expression of BDNF in the spinal cord on the experimental autoimmune encephalomyelitis

Stevanović¹,

Mancic²,

Ilić³

et al. 2019

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Repetitive transcranial magnetic stimulation (rTMS) induces changes in expression of proteins engaged in the activity of excitatory and inhibitory systems, restores these functions and suppresses the progression of disability in experimental autoimmune encephalitis (EAE). The structural type of TMS, the arrangement as theta burst stimulation (TBS) has been applied as intermittent TBS (iTBS) and continuous TBS (cTBS) protocols to female adult DA rats. The animals were randomly divided into experimental groups: control group (C), group treated with complete Freund's adjuvant (CFA), experimental autoimmune encephalomyelitis (EAE) group, group treated with iTBS post EAE immunization (EAE + iTBS), group treated with cTBS post EAE immunization (EAE + cTBS), group of healthy animals treated with iTBS or cTBS. Therapeutic protocols of iTBS or cTBS in all EAE groups of animals were performed starting from 14 days post immunization (dpi), for 10 days with time point decapitation at 24 dpi. After decapitation, spinal cords were analysed for BDNF and Ki67 expression. The results revealed reduced BDNF expression in the rat's spinal cord of EAE animals in the stage of remission, which was associated with increased Ki67 and GFAP expressions. Decreased Iba 1 and BDNF expression, contrary to increased Iba 1 and Ki67 expression, suggests clustered microglia in the resolution phase of EAE. Enhanced GABA expression in spinal cord sections indicates higher GABA metabolic turnover, and also GAD activity in astrocytes, or prominent activity of GABAergic neurons. Both TBS protocols induced advance BDNF expression; amongst iTBS application provoked elevating of BDNF and stabilizing of GFAP and Ki67 expressions.

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“…During the TBS, the rats were slightly stressed and immobilized manually. The coil was gently relied on the rats' head, centring the coil right above bregma [25].…”

Section: Tbs-induced Bdnf Expression In Eaementioning

confidence: 99%

Theta burst stimulation influence the expression of BDNF in the spinal cord on the experimental autoimmune encephalomyelitis

Stevanović¹,

Mancic²,

Ilić³

et al. 2019

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“…These findings are the first to demonstrate changes in glutamate transporter gene expression, and it will be interesting in future studies to isolate RNA from specific cortical regions to assess regional differences and impact on areas within the mesocorticolimbic system such as the NAc. Overall, these studies taken together with others showing regulation of vesicular glutamate transporter I (vGluT1) and GLT1 in the cerebellum following different TBS protocols (Mancic et al, 2016) suggest that glutamate transporters are likely to play an important role in mediating rTMS effects and are worth further investigation as therapeutic targets in addiction.…”

Section: Glutamatergic Systemsmentioning

confidence: 66%

rTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use Disorders

2020

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Cocaine use disorder and methamphetamine use disorder are chronic, relapsing disorders with no US Food and Drug Administration-approved interventions. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation tool that has been increasingly investigated as a possible therapeutic intervention for substance use disorders. rTMS may have the ability to induce beneficial neuroplasticity in abnormal circuits and networks in individuals with addiction. The aim of this review is to highlight the rationale and potential for rTMS to treat cocaine and methamphetamine dependence: we synthesize the outcomes of studies in healthy humans and animal models to identify and understand the neurobiological mechanisms of rTMS that seem most involved in addiction, focusing on the dopaminergic and glutamatergic systems. rTMS-induced changes to neurotransmitter systems include alterations to striatal dopamine release and metabolite levels, as well as to glutamate transporter and receptor expression, which may be relevant for ameliorating the aberrant plasticity observed in individuals with substance use disorders. We also discuss the clinical studies that have used rTMS in humans with cocaine and methamphetamine use disorders. Many such studies suggest changes in network connectivity following acute rTMS, which may underpin reduced craving following chronic rTMS. We suggest several possible future directions for research relating to the therapeutic potential of rTMS in addiction that would help fill current gaps in the literature. Such research would apply rTMS to animal models of addiction, developing a translational pipeline that would guide evidence-based rTMS treatment of cocaine and methamphetamine use disorder.

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“…Nevertheless, neuronal activity is excitatory or inhibitory; it supports neurogenesis through different pathways, such as glutamate uptake and metabolic turnover, oligodendrogenesis, and corticospinal tract remyelination. Besides, TBS associated long-term potentiation or depression widespread through different parts of the brain [9]. Huang YZ et al (2007) showed that human TBS treatment resulted in synaptic plasticity and variations in the activity of cortical inhibitory and excitatory pathways [10,30].…”

Section: Discussionmentioning

confidence: 99%

“…Intermittent TBS induces cortical facilitation, while cTBS causes depression of cortical activity. Both TBS protocols sustain neuronal activity, enabling oligodendrocyte progenitor cell differentiation into oligodendrocytes, and remyelination, eventually [4,9,10].…”

Section: Introductionmentioning

confidence: 99%

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Continuous versus intermittent theta burst stimulation in the treatment of experimental autoimmune encephalomyelitis: a glutamate transporters study

Ninković¹,

Djukić

Mancic³

et al. 2020

Preprint

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Background: Synaptic overload with glutamate aggravates neurotransmission and worsen the progression of the neurodegenerative disease, such as multiple sclerosis (MS). The experimentally induced autoimmune encephalomyelitis (EAE) in rats is a well-established animal model to study MS. Glutamate reuptake occurs by glial glutamate transporter (GLT-1), and glutamate-aspartate transporter (GLAST) localized predominantly in astrocytes terminals. The focus of the study addressing the expression of these transporters in EAE rats and those subjected to theta burst stimulation (TBS), that promotes long-lasting modulation of neuronal activity in rats/humans. Leading by the reported outcomes of TBS, we examined if TBS underlying mechanisms refer to astroglial glutamate transporters status.Methods : We studied changes in the expression of glial glutamate transporter GLT-1 and glutamate-aspartate transporter (GLAST), and glial fibrillary acidic protein (GFAP), in the spinal cord of EAE rats, subjected to intermittent (iTBS) and continuous (cTBS) theta burst stimulation. We quantified the expression of GLAST, GLT-1, and GFAP by immunofluorescence in control and experimental groups of Dark Agouti rats.Results: EAE elevated expression of GFAP, GLAST, and GLT-1. Both TBSs reduced the expression of GFAP. Continual TBS did not interfere with glutamate transporters in EAE rats, while iTBS decreased GLT-1, and increased GLAST.Conclusion: Continual TBS reduced astrogliosis more efficiently than iTBS, in EAE rats. Besides, it did not mitigate the glutamate transporters' expression; thus, glutamate reuptake remained upraised in cTBS exposed EAE rats. Accordingly, we concluded that cTBS might advance the remyelination of damaged neuronal cells in EAE rats. The future clinical trials on the treatment of MS may consider the data of this pre-clinical animal study.

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Transcranial theta-burst stimulation alters GLT-1 and vGluT1 expression in rat cerebellar cortex

Cited by 18 publications

References 57 publications

Theta burst stimulation influence the expression of BDNF in the spinal cord on the experimental autoimmune encephalomyelitis

Theta burst stimulation influence the expression of BDNF in the spinal cord on the experimental autoimmune encephalomyelitis

rTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use Disorders

Continuous versus intermittent theta burst stimulation in the treatment of experimental autoimmune encephalomyelitis: a glutamate transporters study

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