Neurochemical and molecular characteristics of altered brain functional activity in the anti-NMDAR encephalitis
Aims: Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is characterized by widespread neural dysfunction, yet the underlying neurochemical and molecular mechanisms remain poorly understood. This study aimed to investigate whether functional alterations in anti-NMDAR encephalitis are spati...
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Elsevier
2025-10-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996125002669 |
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| author | Xiarong Gong Wei Li Chengsi Luo Yanghua Tian Jiaojian Wang Yuan Gao Yuanyuan Guo Meiling Chen Qiang Meng |
| author_facet | Xiarong Gong Wei Li Chengsi Luo Yanghua Tian Jiaojian Wang Yuan Gao Yuanyuan Guo Meiling Chen Qiang Meng |
| author_sort | Xiarong Gong |
| collection | DOAJ |
| description | Aims: Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is characterized by widespread neural dysfunction, yet the underlying neurochemical and molecular mechanisms remain poorly understood. This study aimed to investigate whether functional alterations in anti-NMDAR encephalitis are spatially associated with neurotransmitter receptor distributions and transcriptomic profiles, to uncover their neurochemical, molecular, and cellular signatures. Methods: A total of 25 patients diagnosed with anti-NMDA receptor encephalitis and 30 healthy controls (HCs) were recruited in this study. All participants underwent resting-state functional MRI (rs-fMRI) scanning, with patients being scanned during the recovery phase of the disease. To explore the neurochemical, molecular and cellular signatures underlying altered brain functional activity, we conducted neuroimaging-neurotransmitter, neuroimaging-transcriptome regression analyses and cell type enrichment analysis, linking aberrant fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) patterns with PET-derived receptor maps and transcriptomic profiles from the Allen Human Brain Atlas (AHBA). Results: Patients exhibited significant alterations in fALFF/ReHo across the frontal, temporal, and occipital cortices. Neuroimaging-neurotransmitter regression analyses revealed that these functional abnormalities were significantly associated with neurotransmitter receptor maps, particularly involving serotonin (5-HT2a) and dopamine (D1) systems. Neuroimaging–transcriptome regression analyses further demonstrated that the genes associated with fALFF/ReHo alterations were primarily enriched in biological processes related to neuron projection development, oligodendrocyte specification and differentiation leading to myelin components for central nervous system. The oligodendrocytes and astrocytes were considered key cellular contributors to the functional alterations. Conclusions: Our findings demonstrate that neural dysfunction during the recovery phase of anti-NMDAR encephalitis are closely linked to neurotransmitter systems and transcriptomic profiles. This multiscale integration bridges molecular mechanisms with neural dysfunction and may inform novel therapeutic strategies. |
| format | Article |
| id | doaj-art-190ec1dba9d945f592a730e0bf58b636 |
| institution | Kabale University |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-190ec1dba9d945f592a730e0bf58b6362025-08-24T05:11:29ZengElsevierNeurobiology of Disease1095-953X2025-10-0121510705010.1016/j.nbd.2025.107050Neurochemical and molecular characteristics of altered brain functional activity in the anti-NMDAR encephalitisXiarong Gong0Wei Li1Chengsi Luo2Yanghua Tian3Jiaojian Wang4Yuan Gao5Yuanyuan Guo6Meiling Chen7Qiang Meng8Department of MR, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, ChinaState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650500, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming 650500, ChinaState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650500, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming 650500, ChinaDepartment of Neurology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, ChinaState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650500, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming 650500, ChinaMedical School, Kunming University of Science and Technology, Kunming 650504, China; Department of Neurology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650034, ChinaDepartment of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of Clinical Psychology, the First People's Hospital of Yunnan Province, Kunming, Yunnan, China; Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, ChinaDepartment of Neurology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650034, China; Correspondence to: Department of Neurology, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, China.Aims: Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is characterized by widespread neural dysfunction, yet the underlying neurochemical and molecular mechanisms remain poorly understood. This study aimed to investigate whether functional alterations in anti-NMDAR encephalitis are spatially associated with neurotransmitter receptor distributions and transcriptomic profiles, to uncover their neurochemical, molecular, and cellular signatures. Methods: A total of 25 patients diagnosed with anti-NMDA receptor encephalitis and 30 healthy controls (HCs) were recruited in this study. All participants underwent resting-state functional MRI (rs-fMRI) scanning, with patients being scanned during the recovery phase of the disease. To explore the neurochemical, molecular and cellular signatures underlying altered brain functional activity, we conducted neuroimaging-neurotransmitter, neuroimaging-transcriptome regression analyses and cell type enrichment analysis, linking aberrant fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) patterns with PET-derived receptor maps and transcriptomic profiles from the Allen Human Brain Atlas (AHBA). Results: Patients exhibited significant alterations in fALFF/ReHo across the frontal, temporal, and occipital cortices. Neuroimaging-neurotransmitter regression analyses revealed that these functional abnormalities were significantly associated with neurotransmitter receptor maps, particularly involving serotonin (5-HT2a) and dopamine (D1) systems. Neuroimaging–transcriptome regression analyses further demonstrated that the genes associated with fALFF/ReHo alterations were primarily enriched in biological processes related to neuron projection development, oligodendrocyte specification and differentiation leading to myelin components for central nervous system. The oligodendrocytes and astrocytes were considered key cellular contributors to the functional alterations. Conclusions: Our findings demonstrate that neural dysfunction during the recovery phase of anti-NMDAR encephalitis are closely linked to neurotransmitter systems and transcriptomic profiles. This multiscale integration bridges molecular mechanisms with neural dysfunction and may inform novel therapeutic strategies.http://www.sciencedirect.com/science/article/pii/S0969996125002669Anti-NMDAR encephalitisResting-state fMRI (rs-fMRI)Regional homogeneity (ReHo)Fractional amplitude of low-frequency fluctuations (fALFF)NeurotransmittersAllen human brain atlas |
| spellingShingle | Xiarong Gong Wei Li Chengsi Luo Yanghua Tian Jiaojian Wang Yuan Gao Yuanyuan Guo Meiling Chen Qiang Meng Neurochemical and molecular characteristics of altered brain functional activity in the anti-NMDAR encephalitis Neurobiology of Disease Anti-NMDAR encephalitis Resting-state fMRI (rs-fMRI) Regional homogeneity (ReHo) Fractional amplitude of low-frequency fluctuations (fALFF) Neurotransmitters Allen human brain atlas |
| title | Neurochemical and molecular characteristics of altered brain functional activity in the anti-NMDAR encephalitis |
| title_full | Neurochemical and molecular characteristics of altered brain functional activity in the anti-NMDAR encephalitis |
| title_fullStr | Neurochemical and molecular characteristics of altered brain functional activity in the anti-NMDAR encephalitis |
| title_full_unstemmed | Neurochemical and molecular characteristics of altered brain functional activity in the anti-NMDAR encephalitis |
| title_short | Neurochemical and molecular characteristics of altered brain functional activity in the anti-NMDAR encephalitis |
| title_sort | neurochemical and molecular characteristics of altered brain functional activity in the anti nmdar encephalitis |
| topic | Anti-NMDAR encephalitis Resting-state fMRI (rs-fMRI) Regional homogeneity (ReHo) Fractional amplitude of low-frequency fluctuations (fALFF) Neurotransmitters Allen human brain atlas |
| url | http://www.sciencedirect.com/science/article/pii/S0969996125002669 |
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