Dataset Information

Plasma BDNF Levels Following Transcranial Direct Current Stimulation Allow Prediction of Synaptic Plasticity and Memory Deficits in 3×Tg-AD Mice.

ABSTRACT: Early diagnosis of Alzheimer's disease (AD) supposedly increases the effectiveness of therapeutic interventions. However, presently available diagnostic procedures are either invasive or require complex and expensive technologies, which cannot be applied at a larger scale to screen populations at risk of AD. We were looking for a biomarker allowing to unveil a dysfunction of molecular mechanisms, which underly synaptic plasticity and memory, before the AD phenotype is manifested and investigated the effects of transcranial direct current stimulation (tDCS) in 3×Tg-AD mice, an experimental model of AD which does not exhibit any long-term potentiation (LTP) and memory deficits at the age of 3 months (3×Tg-AD-3M). Our results demonstrated that tDCS differentially affected 3×Tg-AD-3M and age-matched wild-type (WT) mice. While tDCS increased LTP at CA3-CA1 synapses and memory in WT mice, it failed to elicit these effects in 3×Tg-AD-3M mice. Remarkably, 3×Tg-AD-3M mice did not show the tDCS-dependent increases in pCREB Ser133 and pCaMKII Thr286 , which were found in WT mice. Of relevance, tDCS induced a significant increase of plasma BDNF levels in WT mice, which was not found in 3×Tg-AD-3M mice. Collectively, our results showed that plasticity mechanisms are resistant to tDCS effects in the pre-AD stage. In particular, the lack of BDNF responsiveness to tDCS in 3×Tg-AD-3M mice suggests that combining tDCS with dosages of plasma BDNF levels may provide an easy-to-detect and low-cost biomarker of covert impairment of synaptic plasticity mechanisms underlying memory, which could be clinically applicable. Testing proposed here might be useful to identify AD in its preclinical stage, allowing timely and, hopefully, more effective disease-modifying interventions.

SUBMITTER: Cocco S

PROVIDER: S-EPMC7349675 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Plasma BDNF Levels Following Transcranial Direct Current Stimulation Allow Prediction of Synaptic Plasticity and Memory Deficits in 3×Tg-AD Mice.

Cocco Sara S Rinaudo Marco M Fusco Salvatore S Longo Valentina V Gironi Katia K Renna Pietro P Aceto Giuseppe G Mastrodonato Alessia A Li Puma Domenica Donatella DD Podda Maria Vittoria MV Grassi Claudio C

Frontiers in cell and developmental biology 20200703

Early diagnosis of Alzheimer's disease (AD) supposedly increases the effectiveness of therapeutic interventions. However, presently available diagnostic procedures are either invasive or require complex and expensive technologies, which cannot be applied at a larger scale to screen populations at risk of AD. We were looking for a biomarker allowing to unveil a dysfunction of molecular mechanisms, which underly synaptic plasticity and memory, before the AD phenotype is manifested and investigated ...[more]

PMID: 32719795

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Project description:Transcranial direct current stimulation (tDCS) is a promising method for altering cortical excitability with clinical implications in neuropsychiatric diseases. Its application in neurodevelopmental disorders especially attention-deficit hyperactivity disorder (ADHD), is in early stage and promising but its effectiveness has not been systematically examined yet. We conducted a meta-analysis on the effectiveness of tDCS on the most studied neuropsychological symptoms of ADHD, which is the first reported meta-analysis of tDCS studies on ADHD. Data from 10 randomized controlled studies (including 11 separate experiments) targeting inhibitory control, and/or working memory (WM) in ADHD were included. Results show that overall tDCS significantly improved inhibitory control. Sub-analyses further show that dorsolateral prefrontal cortex (dlPFC) (but not right inferior frontal gyrus) tDCS and anodal (but not cathodal) tDCS significantly improved inhibitory control with a small effect size. Anodal dlPFC-tDCS had the largest significant effect on inhibitory control with a small-to-medium effect size. Additionally, a significant improving effect of tDCS on inhibitory control accuracy (but not response time) and WM speed (but not accuracy) were found. Overall, this meta-analysis supports a beneficial effect of tDCS on inhibitory control and WM in ADHD with a small-to-medium effect size. TDCS seems to be a promising method for improving neuropsychological and cognitive deficits in ADHD. However, there might be a dissociation between neuropsychological deficits and clinical symptoms of ADHD and therefore, the significance of this meta-analysis for clinical purposes is limited. Future studies should systematically evaluate the role of inter-individual factors (i.e., ADHD subtype, types of the deficit) and stimulation parameters (i.e., site, polarity, intensity, duration, repetition rate) on tDCS efficacy in ADHD population and examine whether benefits are long-term.

Dataset Information

Plasma BDNF Levels Following Transcranial Direct Current Stimulation Allow Prediction of Synaptic Plasticity and Memory Deficits in 3×Tg-AD Mice.

Publications

Plasma BDNF Levels Following Transcranial Direct Current Stimulation Allow Prediction of Synaptic Plasticity and Memory Deficits in 3×Tg-AD Mice.

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