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慢性紫外线照射通过多巴胺通路的失调诱导记忆缺陷。

Chronic ultraviolet irradiation induces memory deficits via dysregulation of the dopamine pathway.

机构信息

Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea.

Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.

出版信息

Exp Mol Med. 2024 Jun;56(6):1401-1411. doi: 10.1038/s12276-024-01242-x. Epub 2024 Jun 3.

DOI:10.1038/s12276-024-01242-x
PMID:38825641
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11263540/
Abstract

The effects of ultraviolet (UV) radiation on brain function have previously been investigated; however, the specific neurotransmitter-mediated mechanisms responsible for UV radiation-induced neurobehavioral changes remain elusive. In this study, we aimed to explore the mechanisms underlying UV radiation-induced neurobehavioral changes. In a mouse model, we observed that UV irradiation of the skin induces deficits in hippocampal memory, synaptic plasticity, and adult neurogenesis, as well as increased dopamine levels in the skin, adrenal glands, and brain. Chronic UV exposure altered the expression of genes involved in dopaminergic neuron differentiation. Furthermore, chronic peripheral dopamine treatments resulted in memory deficits. Systemic administration of a dopamine D1/D5 receptor antagonist reversed changes in memory, synaptic plasticity, adult neurogenesis, and gene expression in UV-irradiated mice. Our findings provide converging evidence that chronic UV exposure alters dopamine levels in the central nervous system and peripheral organs, including the skin, which may underlie the observed neurobehavioral shifts, such as hippocampal memory deficits and impaired neurogenesis. This study underscores the importance of protection from UV exposure and introduces the potential of pharmacological approaches targeting dopamine receptors to counteract the adverse neurological impacts of UV exposure.

摘要

紫外线 (UV) 辐射对大脑功能的影响此前已有研究;然而,导致 UV 辐射引起的神经行为变化的确切神经递质介导机制仍不清楚。在本研究中,我们旨在探讨 UV 辐射引起的神经行为变化的机制。在小鼠模型中,我们观察到皮肤的 UV 照射会导致海马记忆、突触可塑性和成年神经发生受损,以及皮肤、肾上腺和大脑中的多巴胺水平升高。慢性 UV 暴露改变了参与多巴胺能神经元分化的基因的表达。此外,慢性外周多巴胺处理会导致记忆缺陷。系统给予多巴胺 D1/D5 受体拮抗剂可逆转 UV 照射小鼠的记忆、突触可塑性、成年神经发生和基因表达的变化。我们的研究结果提供了一致的证据,表明慢性 UV 暴露会改变中枢神经系统和外周器官(包括皮肤)中的多巴胺水平,这可能是观察到的神经行为变化(如海马记忆缺陷和神经发生受损)的基础。这项研究强调了保护免受 UV 照射的重要性,并提出了针对多巴胺受体的药理学方法的潜力,以抵消 UV 照射对神经系统的不利影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdb4/11263540/25ea7dffe1b6/12276_2024_1242_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdb4/11263540/a945c90a6f16/12276_2024_1242_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdb4/11263540/06017c3cec26/12276_2024_1242_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdb4/11263540/616a81227901/12276_2024_1242_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdb4/11263540/6b91cdf0fb22/12276_2024_1242_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdb4/11263540/a35c6638e91b/12276_2024_1242_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdb4/11263540/25ea7dffe1b6/12276_2024_1242_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdb4/11263540/a945c90a6f16/12276_2024_1242_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdb4/11263540/06017c3cec26/12276_2024_1242_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdb4/11263540/616a81227901/12276_2024_1242_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdb4/11263540/6b91cdf0fb22/12276_2024_1242_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdb4/11263540/a35c6638e91b/12276_2024_1242_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdb4/11263540/25ea7dffe1b6/12276_2024_1242_Fig6_HTML.jpg

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