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 x 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 x Tg-AD-3M). Our results demonstrated that tDCS differentially affected 3 x 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 x Tg-AD-3M mice. Remarkably, 3 x Tg-AD-3M mice did not show the tDCS-dependent increases in pCREBSer133 and pCaMKIIThr286, 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 x 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 x Tg-AD-3M mice suggests that combining tDCS with dosages of plasma BDNF levels may provide an easy-todetect 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.

Cocco, S., Rinaudo, M., Fusco, S., Longo, V., Gironi, K., Renna, P., Aceto, G., Mastrodonato, A., Puma., L., Podda, M. V., Grassi, C., Plasma BDNF levels following transcranial direct current stimulation allow prediction of synaptic plasticity and memory deficits in 3×Tg-AD mice., <<FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY>>, 2020; 2020 (8): N/A-N/A. [doi:10.3389/fcell.2020.00541] [http://hdl.handle.net/10807/157884]

Plasma BDNF levels following transcranial direct current stimulation allow prediction of synaptic plasticity and memory deficits in 3×Tg-AD mice.

Cocco, S.;Rinaudo, M.;Fusco, S.;Longo, V.;Gironi, K.;Renna, P.;Aceto, G.;Mastrodonato, A.;Puma., Li;Podda, Maria Vittoria
Penultimo
;
Grassi, C.
2020

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 x 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 x Tg-AD-3M). Our results demonstrated that tDCS differentially affected 3 x 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 x Tg-AD-3M mice. Remarkably, 3 x Tg-AD-3M mice did not show the tDCS-dependent increases in pCREBSer133 and pCaMKIIThr286, 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 x 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 x Tg-AD-3M mice suggests that combining tDCS with dosages of plasma BDNF levels may provide an easy-todetect 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.
Inglese
Cocco, S., Rinaudo, M., Fusco, S., Longo, V., Gironi, K., Renna, P., Aceto, G., Mastrodonato, A., Puma., L., Podda, M. V., Grassi, C., Plasma BDNF levels following transcranial direct current stimulation allow prediction of synaptic plasticity and memory deficits in 3×Tg-AD mice., <<FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY>>, 2020; 2020 (8): N/A-N/A. [doi:10.3389/fcell.2020.00541] [http://hdl.handle.net/10807/157884]
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