Treating hippocampal neural stem cells with nano-pulsed laser therapy generates neurons resilient against amyloid-β oligomer toxicity

Background: Hippocampal synaptic dysfunction driven by toxic amyloid-β oligomers (AβO) is an early event in the progression of neurodegeneration and cognitive decline in Alzheimer's disease (AD). Non-invasive photobiomodulation therapy (PBM) is a promising intervention that has been shown to reduce amyloid and tau pathology, improve synaptic function, and preserve hippocampal neurogenesis in animal models of AD. Nano-pulsed laser therapy (NPLT) is a type of PBM therapy using pulsed 808 nm near-infrared laser light and optoacoustically generated ultrasound waves to stimulate deeper brain structures than would be accessible by traditional PBM therapy. We hypothesize that NPLT can effectively modulate hippocampal neurogenesis to induce resilience against AD. Objective: To assess resilience of hippocampal neurons derived from NPLT-treated neural stem cells (NSC) against AβO toxicity. Methods: We use NPLT to stimulate adult hippocampal neural stem cells (NSC) then induce neuronal differentiation in vitro and assess the mature neurons for AβO binding capacity and mitochondrial toxicity, and gene expression changes after NPLT. Results: We found that neurons differentiated from NPLT-treated NSC are resilient against AβO binding and mitochondrial toxicity, and show increased expression of genes associated with autophagy and proteostasis. Conclusions: Our findings support the hypothesis that NPLT modulation of hippocampal neurogenesis can be an effective non-invasive approach to induce resilience against AD toxic oligomers.