Transcranial direct current stimulation (tDCS) Intervention in 5xFAD Mice: Reduction of Amyloid-Beta Levels and Restoration of Evoked Gamma-Band Oscillations Through Perineuronal Net Protection

Abstract

This study investigates the potential therapeutic effects of transcranial direct current stimulation (tDCS) on various aspects of Alzheimer's disease (AD), including amyloidopathy, gliopathy, perineuronal nets (PNNs), and gamma-band oscillations (GBO). The findings suggest that tDCS may have a beneficial impact on these factors in the context of AD. First, tDCS was found to reduce the area and number of amyloid-beta (Aβ) plaques in the hippocampus and prefrontal cortex of transgenic AD mice, indicating a potential role in attenuating amyloidopathy. This reduction in Aβ plaques suggests a promising avenue for AD therapeutic interventions. Second, the study observed an enhancement of astrocyte levels in the hippocampus and prefrontal cortex of AD mice following tDCS. Astrocytes are known to play a role in amyloid plaque clearance, suggesting that tDCS may modulate gliopathy and contribute to the clearance of aberrant amyloid accumulation. Third, tDCS was associated with the restoration of perineuronal nets (PNNs), particularly in the hippocampus, which are important for stabilizing neural circuits. Preserving PNNs may reduce the loss of parvalbumin-positive (PV) interneurons and mitigate cognitive deficits in AD. Furthermore, the study found evidence of tDCS-induced restoration of gamma-band oscillations (GBO) in the frontal region of AD mice. GBO is linked to various cognitive functions, and its restoration may have a positive impact on cognitive performance in AD. Behavioral tests, including the Open Field Test (OFT), Novel Place Recognition (NPR) test, and Y-maze test, did not reveal significant differences in locomotor function or visuospatial memory between tDCS-treated and sham-treated AD mice. However, the study acknowledges limitations, including potential regional specificity of tDCS effects, uncertain functional implications of increased astrocytes, and concerns related to participant safety and data variability.Overall, this study provides compelling evidence that tDCS may hold promise as a therapeutic intervention for AD by addressing amyloidopathy, gliopathy, PNN preservation, and the restoration of GBO. Further research is needed to fully elucidate the mechanisms and clinical applicability of tDCS in the context of AD.