Terahertz photoneuromodulation of lateral orbitofrontal cortex neurons ameliorates stress-induced depression and cognitive impairment

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 i...

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Main Authors: Yuanyuan He, Jing Ma, Yun Yu, Junkai Yin, Ge Gao, Yifang Yuan, Hao Ruan, Xueqing Yan, Zihua Song, Chao Chang
Format: Article
Language:English
Published: KeAi Communications Co. Ltd. 2025-03-01
Series:Fundamental Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667325824005247
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author Yuanyuan He
Jing Ma
Yun Yu
Junkai Yin
Ge Gao
Yifang Yuan
Hao Ruan
Xueqing Yan
Zihua Song
Chao Chang
author_facet Yuanyuan He
Jing Ma
Yun Yu
Junkai Yin
Ge Gao
Yifang Yuan
Hao Ruan
Xueqing Yan
Zihua Song
Chao Chang
author_sort Yuanyuan He
collection DOAJ
description 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 (OFCGlu) 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.
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publishDate 2025-03-01
publisher KeAi Communications Co. Ltd.
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spelling doaj-art-e34b9f6749524c7cb6c037e8f0912e722025-08-20T02:10:09ZengKeAi Communications Co. Ltd.Fundamental Research2667-32582025-03-015260261110.1016/j.fmre.2024.12.004Terahertz photoneuromodulation of lateral orbitofrontal cortex neurons ameliorates stress-induced depression and cognitive impairmentYuanyuan He0Jing Ma1Yun Yu2Junkai Yin3Ge Gao4Yifang Yuan5Hao Ruan6Xueqing Yan7Zihua Song8Chao Chang9State 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; School of Safety Engineering, North China Institute of Science and Technology, Hebei 065201, ChinaInnovation Laboratory of Terahertz Biophysics, National Innovation Institute of Defense Technology, Beijing 100071, ChinaInnovation Laboratory of Terahertz Biophysics, National Innovation Institute of Defense Technology, Beijing 100071, ChinaInnovation Laboratory of Terahertz Biophysics, National Innovation Institute of Defense Technology, Beijing 100071, ChinaSchool of Life Science, Tsinghua University, Beijing 100084, ChinaInnovation Laboratory of Terahertz Biophysics, National Innovation Institute of Defense Technology, Beijing 100071, ChinaInnovation Laboratory of Terahertz Biophysics, National Innovation Institute of Defense Technology, Beijing 100071, ChinaState Key Laboratory of NPT, and Key Laboratory of HEDP of MoE, CAPT, Peking University, Beijing 100871, China; Corresponding authors.Innovation Laboratory of Terahertz Biophysics, National Innovation Institute of Defense Technology, Beijing 100071, China; Corresponding authors.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; Corresponding authors.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 (OFCGlu) 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.http://www.sciencedirect.com/science/article/pii/S2667325824005247Terahertz photoneuromodulationDepressionCognitive impairmentOrbitofrontal cortexSelective serotonin reuptake inhibitors
spellingShingle Yuanyuan He
Jing Ma
Yun Yu
Junkai Yin
Ge Gao
Yifang Yuan
Hao Ruan
Xueqing Yan
Zihua Song
Chao Chang
Terahertz photoneuromodulation of lateral orbitofrontal cortex neurons ameliorates stress-induced depression and cognitive impairment
Fundamental Research
Terahertz photoneuromodulation
Depression
Cognitive impairment
Orbitofrontal cortex
Selective serotonin reuptake inhibitors
title Terahertz photoneuromodulation of lateral orbitofrontal cortex neurons ameliorates stress-induced depression and cognitive impairment
title_full Terahertz photoneuromodulation of lateral orbitofrontal cortex neurons ameliorates stress-induced depression and cognitive impairment
title_fullStr Terahertz photoneuromodulation of lateral orbitofrontal cortex neurons ameliorates stress-induced depression and cognitive impairment
title_full_unstemmed Terahertz photoneuromodulation of lateral orbitofrontal cortex neurons ameliorates stress-induced depression and cognitive impairment
title_short Terahertz photoneuromodulation of lateral orbitofrontal cortex neurons ameliorates stress-induced depression and cognitive impairment
title_sort terahertz photoneuromodulation of lateral orbitofrontal cortex neurons ameliorates stress induced depression and cognitive impairment
topic Terahertz photoneuromodulation
Depression
Cognitive impairment
Orbitofrontal cortex
Selective serotonin reuptake inhibitors
url http://www.sciencedirect.com/science/article/pii/S2667325824005247
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