Near-Infrared Light Induces Neurogenesis and Modulates Anxiety-like Behavior

Abstract Background The hippocampus is associated with mood disorders, and the activation of quiescent neurogenesis has been linked to anxiolytic effects. Near-infrared (NIR) light has shown potential to improve learning and memory in human and animal models. Despite the vast amount of information regarding the effect of visible light, there is a significant gap in our understanding of the response of neural stem cells (NSCs) to NIR stimulation, particularly in anxiety-like behavior. The present study aimed to develop a new optical manipulation approach to stimulate hippocampal neurogenesis and understand the mechanisms underlying its anxiolytic effects. Methods We used 940 nm NIR (40 Hz) light exposure to stimulate hippocampal stem cells in C57BL/6 mice. The enhanced proliferation and astrocyte differentiation of NIR-treated NSCs were assessed using 5-Ethynyl-2’-deoxyuridine (EdU) incorporation and immunofluorescence assays. Additionally, we evaluated calcium activity of NIR light-treated astrocytes using GCaMP6f recording through fluorescence fiber photometry. The effects of NIR illumination of the hippocampus on anxiety-like behaviors were evaluated using elevated plus maze and open-field test. Results In vitro, the NIR light effectively promoted the NSC proliferation and astrocyte differentiation via the Opn4 photoreceptor. In vivo, the NIR stimulation significantly enhanced neurogenesis and calcium-dependent astrocytic activity. Moreover, activating hippocampal astrocytes with 40-Hz NIR light substantially improved anxiety-like behaviors in mice. Conclusions We found that flickering NIR (940 nm/40Hz) light illumination improved neurogenesis in the hippocampus with anxiolytic effects. This innovative approach holds promise as a novel preventive treatment for depression.