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      Near-infrared light induces neurogenesis and modulates anxiety-like behavior

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          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 regarding 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

          NIR light effectively promoted NSC proliferation and astrocyte differentiation via the OPN4 photoreceptor. Furthermore, 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.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13287-024-04114-3.

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          Most cited references27

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          Memory, navigation and theta rhythm in the hippocampal-entorhinal system.

          Theories on the functions of the hippocampal system are based largely on two fundamental discoveries: the amnestic consequences of removing the hippocampus and associated structures in the famous patient H.M. and the observation that spiking activity of hippocampal neurons is associated with the spatial position of the rat. In the footsteps of these discoveries, many attempts were made to reconcile these seemingly disparate functions. Here we propose that mechanisms of memory and planning have evolved from mechanisms of navigation in the physical world and hypothesize that the neuronal algorithms underlying navigation in real and mental space are fundamentally the same. We review experimental data in support of this hypothesis and discuss how specific firing patterns and oscillatory dynamics in the entorhinal cortex and hippocampus can support both navigation and memory.
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            Gamma frequency entrainment attenuates amyloid load and modifies microglia.

            Changes in gamma oscillations (20-50 Hz) have been observed in several neurological disorders. However, the relationship between gamma oscillations and cellular pathologies is unclear. Here we show reduced, behaviourally driven gamma oscillations before the onset of plaque formation or cognitive decline in a mouse model of Alzheimer's disease. Optogenetically driving fast-spiking parvalbumin-positive (FS-PV)-interneurons at gamma (40 Hz), but not other frequencies, reduces levels of amyloid-β (Aβ)1-40 and Aβ 1-42 isoforms. Gene expression profiling revealed induction of genes associated with morphological transformation of microglia, and histological analysis confirmed increased microglia co-localization with Aβ. Subsequently, we designed a non-invasive 40 Hz light-flickering regime that reduced Aβ1-40 and Aβ1-42 levels in the visual cortex of pre-depositing mice and mitigated plaque load in aged, depositing mice. Our findings uncover a previously unappreciated function of gamma rhythms in recruiting both neuronal and glial responses to attenuate Alzheimer's-disease-associated pathology.
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              Phototransduction by retinal ganglion cells that set the circadian clock.

              Light synchronizes mammalian circadian rhythms with environmental time by modulating retinal input to the circadian pacemaker-the suprachiasmatic nucleus (SCN) of the hypothalamus. Such photic entrainment requires neither rods nor cones, the only known retinal photoreceptors. Here, we show that retinal ganglion cells innervating the SCN are intrinsically photosensitive. Unlike other ganglion cells, they depolarized in response to light even when all synaptic input from rods and cones was blocked. The sensitivity, spectral tuning, and slow kinetics of this light response matched those of the photic entrainment mechanism, suggesting that these ganglion cells may be the primary photoreceptors for this system.
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                Author and article information

                Contributors
                liuduo@sdu.edu.cn
                liusw@sdu.edu.cn
                liuqiji@sdu.edu.cn
                lixi@sdu.edu.cn
                Journal
                Stem Cell Res Ther
                Stem Cell Res Ther
                Stem Cell Research & Therapy
                BioMed Central (London )
                1757-6512
                20 December 2024
                20 December 2024
                2024
                : 15
                : 494
                Affiliations
                [1 ]Key Laboratory of Experimental Teratology of the Ministry of Education, Department of Medical Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, ( https://ror.org/0207yh398) Jinan, Shandong 250012 China
                [2 ]Department of Anatomy and Neurobiology, Research Center for Sectional and Imaging Anatomy, Shandong Provincial Key Laboratory of Mental Disorder, Shandong Key Laboratory of Digital Human and Clinical Anatomy, School of Basic Medical Sciences, Cheeloo College of Medicine, Institute of Brain and Brain-Inspired Science, Shandong University, Shandong University, ( https://ror.org/0207yh398) Jinan, Shandong 250012 China
                [3 ]School of Sports Leisure, Shandong Sport University, ( https://ror.org/026b4k258) Jinan, Shandong 250102 China
                [4 ]Institute of Novel Semiconductors, State Key Laboratory of Crystal Materials, Shandong University, ( https://ror.org/0207yh398) Jinan, Shandong 250100 China
                [5 ]School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, Shandong 266071 China
                Author information
                http://orcid.org/0000-0003-2912-5803
                Article
                4114
                10.1186/s13287-024-04114-3
                11662543
                39707549
                54b283e0-6bd3-45e9-916d-ebbcc2d41e6a
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

                History
                : 2 February 2024
                : 12 December 2024
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81873737
                Award ID: 32070586
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100007129, Natural Science Foundation of Shandong Province;
                Award ID: ZR2022LZL010
                Award Recipient :
                Categories
                Research
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                © BioMed Central Ltd., part of Springer Nature 2024

                Molecular medicine
                neural stem cells,nir light,anxiety,astrocytes,calcium activity
                Molecular medicine
                neural stem cells, nir light, anxiety, astrocytes, calcium activity

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