Autor(es): Monteiro, Francisca ; Oliveira, Sofia ; Marques, Carlos ; Papadimitriou, Georgia ; Silva, Joana M. ; Padrão, Jorge ; Sotiropoulos, Ioannis ; Catarino, Susana ; Silva, Filipe S. ; Carvalho, Óscar
Data: 2025
Identificador Persistente: https://hdl.handle.net/1822/94502
Origem: RepositóriUM - Universidade do Minho
Assunto(s): Alzheimer’s disease; Transcranial photobiomodulation; Transcranial ultrasound stimulation; Optimization study
The effectiveness of transcranial photobiomodulation (tPBM) and ultrasound stimulation (tUS) to mitigate different neuropathological mechanisms and stimulate neuroprotective responses has been vastly demonstrated in preclinical disease models. However, the translation into clinics is still suboptimal, revealing the need for more solid basic research to ascertain the most effective stimulation parameters to modulate the neuronal response to therapeutic light and ultrasound. Also, the great discourse among the tPBM and tUS protocols currently administered confirms the urge to optimize their parameterization. This certainly depends on the neuropathological traits of each specific neurological disorder and therefore requires the establishment of different stimulation protocols for distinct brain diseases. Here, we describe a thorough optimization study to define the best tPBM and tUS parameters to block the neuropathological mechanisms of Alzheimer’s disease (AD), a deadly and uncurable neurodegenerative disorder that represents the most common cause of dementia worldwide. For that, mouse neuroblastoma (N2a) cells expressing AD-associated mutations (i.e., APPSwe and Tau P301L) were used to assess the bioeffects of different levels of PBM and US. Different wavelengths (PBM) or central frequencies (US), pulsing frequencies, power densities, treatment durations, and periodicities were tested. Five-minute sessions were delivered each day. The protocols associated with the greatest improvements in neuronal activity were progressively selected and their ability to block Aβ and Tau pathologies was assessed. By adopting this methodology, we conducted a pioneer optimization of PBM and US parameters, from which the best protocols to stimulate the Alzheimer’s disease brain were settled. We believe these optimization studies will fill the translatability gap and pave the way for an effective clinical application of both tPBM and tUS to treat AD in forthcoming years. This work will also be the launching pad for the development of optimized stimulation protocols for a broad range of neurological diseases.
