He Yuanyuan, Ma Jing, Yu Yun, Yin Junkai, Gao Ge, Yuan Yifang, Ruan Hao, Yan Xueqing, Song Zihua, Chang Chao
State Key Laboratory of NPT, and Key Laboratory of HEDP of MoE, CAPT, Peking University, Beijing 100871, China.
Innovation Laboratory of Terahertz Biophysics, National Innovation Institute of Defense Technology, Beijing 100071, China.
Fundam Res. 2024 Dec 19;5(2):602-611. doi: 10.1016/j.fmre.2024.12.004. eCollection 2025 Mar.
Depression imposes a staggering global socioeconomic burden. Current pharmacotherapies face major limitations, including slow efficacy, adverse effects, and non-response rates of up to 55%, necessitating novel therapeutic modalities. This study introduces terahertz (THz) photoneuromodulation as an innovative physical intervention for depression, offering several advantages over conventional pharmacological or optogenetic approaches. Mild THz photoneuromodulation circumvents the need for exogenous agents or genetic modifications, mitigating potential risks while precisely modulating neurotransmitter levels and neuronal excitability to alleviate depression-like behaviors. In a chronic restraint stress (CRS) mouse model, THz photostimulation rapidly attenuated hyperactivity and increased serotonin levels by 107.5% ± 45.3% in lateral orbitofrontal cortex glutamatergic neurons (OFC) compared to those treated with antidepressants. This led to marked improvements in depressive-like behaviors and cognitive function. Furthermore, THz modulation of OFC activity recapitulated the effects of chemogenetic inhibition, underscoring the OFC's pivotal role in regulating depressive states. This research unveils THz photoneuromodulation as a promising, safe, rapid-acting, and durable neurotherapeutic strategy addressing persistent unmet needs in depression treatment.
抑郁症给全球带来了惊人的社会经济负担。目前的药物治疗面临重大局限性，包括疗效缓慢、副作用以及高达55%的无反应率，因此需要新的治疗方式。本研究引入太赫兹（THz）光神经调节作为一种治疗抑郁症的创新性物理干预手段，与传统的药理学或光遗传学方法相比具有诸多优势。温和的太赫兹光神经调节无需外源性药物或基因改造，在精确调节神经递质水平和神经元兴奋性以减轻类似抑郁行为的同时，降低了潜在风险。在慢性束缚应激（CRS）小鼠模型中，与接受抗抑郁药物治疗的小鼠相比，太赫兹光刺激迅速减弱了小鼠的多动行为，并使外侧眶额皮质谷氨酸能神经元（OFC）中的血清素水平提高了107.5%±45.3%。这导致了类似抑郁行为和认知功能的显著改善。此外，太赫兹对OFC活动的调节重现了化学遗传学抑制的效果，强调了OFC在调节抑郁状态中的关键作用。这项研究揭示了太赫兹光神经调节是一种有前景、安全、速效且持久的神经治疗策略，可满足抑郁症治疗中持续未被满足的需求。
