{"title":"间歇Theta脉冲刺激小脑通过cAMP/PKA/CREB通路促进脑卒中后抑郁的神经系统恢复","authors":"Xue Yang, Tengmin Gui, Shuxian Zhang, Tianling Wang, Xueting Chen, Huanhuan Ren, Chunyan Xu, Dingwei He, Liqing Yao","doi":"10.1161/STROKEAHA.124.048697","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Stroke causes somatic dysfunction and psychological disorders, leading to poststroke depression (PSD). This study investigates mood alterations in PSD models via cerebellar intermittent theta burst stimulation (iTBS).</p><p><strong>Methods: </strong>PSD animal models were developed using middle cerebral artery occlusion and chronic unpredictable mild stress procedures. PSD models underwent cerebellar iTBS with different pulse numbers. Neurological recovery was evaluated using open-field test, sucrose preference test, forced swimming test, and balance beam test. Golgi and hematoxylin-eosin staining assessed neuronal repair, while quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and Western blotting evaluated effects on BDNF (brain-derived neurotrophic factor), hypothalamic-pituitary-adrenal axis factors, and the cAMP/PKA (protein kinase A)/CREB (cAMP-response element-binding protein) pathway. The study first determined the effects of different intensities of iTBS stimulation on neurological recovery in PSD rats. Second, the effects of iTBS stimulation on the cAMP/PKA/CREB pathway were verified using adenoviral blockade of PKA and CREB at iTBS-1800.</p><p><strong>Results: </strong>PSD models showed decreased vertical movement, locomotor distance, and sucrose preference and increased immobility time and balance beam test score, which were reversed by iTBS. iTBS increased dendritic length and spine density in Purkinje cells, alleviated neuronal damage in multiple brain regions, and enhanced BDNF synthesis. It also regulated adrenocorticotropic hormone, cortisol, and GR (glucocorticoid receptor) expression, and activated the cAMP/PKA/CREB pathway.</p><p><strong>Conclusions: </strong>Cerebellar iTBS improves PSD by activating the cAMP-PKA/CREB pathway, increasing BDNF, and reducing hypothalamic-pituitary-adrenal axis hyperactivity, suggesting potential for human PSD treatment.</p>","PeriodicalId":21989,"journal":{"name":"Stroke","volume":" ","pages":""},"PeriodicalIF":7.8000,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Intermittent Theta Burst Stimulation Over Cerebellum Facilitates Neurological Recovery in Poststroke Depression via the cAMP/PKA/CREB Pathway.\",\"authors\":\"Xue Yang, Tengmin Gui, Shuxian Zhang, Tianling Wang, Xueting Chen, Huanhuan Ren, Chunyan Xu, Dingwei He, Liqing Yao\",\"doi\":\"10.1161/STROKEAHA.124.048697\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Stroke causes somatic dysfunction and psychological disorders, leading to poststroke depression (PSD). This study investigates mood alterations in PSD models via cerebellar intermittent theta burst stimulation (iTBS).</p><p><strong>Methods: </strong>PSD animal models were developed using middle cerebral artery occlusion and chronic unpredictable mild stress procedures. PSD models underwent cerebellar iTBS with different pulse numbers. Neurological recovery was evaluated using open-field test, sucrose preference test, forced swimming test, and balance beam test. Golgi and hematoxylin-eosin staining assessed neuronal repair, while quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and Western blotting evaluated effects on BDNF (brain-derived neurotrophic factor), hypothalamic-pituitary-adrenal axis factors, and the cAMP/PKA (protein kinase A)/CREB (cAMP-response element-binding protein) pathway. The study first determined the effects of different intensities of iTBS stimulation on neurological recovery in PSD rats. Second, the effects of iTBS stimulation on the cAMP/PKA/CREB pathway were verified using adenoviral blockade of PKA and CREB at iTBS-1800.</p><p><strong>Results: </strong>PSD models showed decreased vertical movement, locomotor distance, and sucrose preference and increased immobility time and balance beam test score, which were reversed by iTBS. iTBS increased dendritic length and spine density in Purkinje cells, alleviated neuronal damage in multiple brain regions, and enhanced BDNF synthesis. It also regulated adrenocorticotropic hormone, cortisol, and GR (glucocorticoid receptor) expression, and activated the cAMP/PKA/CREB pathway.</p><p><strong>Conclusions: </strong>Cerebellar iTBS improves PSD by activating the cAMP-PKA/CREB pathway, increasing BDNF, and reducing hypothalamic-pituitary-adrenal axis hyperactivity, suggesting potential for human PSD treatment.</p>\",\"PeriodicalId\":21989,\"journal\":{\"name\":\"Stroke\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":7.8000,\"publicationDate\":\"2025-03-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Stroke\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1161/STROKEAHA.124.048697\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Stroke","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1161/STROKEAHA.124.048697","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Intermittent Theta Burst Stimulation Over Cerebellum Facilitates Neurological Recovery in Poststroke Depression via the cAMP/PKA/CREB Pathway.
Background: Stroke causes somatic dysfunction and psychological disorders, leading to poststroke depression (PSD). This study investigates mood alterations in PSD models via cerebellar intermittent theta burst stimulation (iTBS).
Methods: PSD animal models were developed using middle cerebral artery occlusion and chronic unpredictable mild stress procedures. PSD models underwent cerebellar iTBS with different pulse numbers. Neurological recovery was evaluated using open-field test, sucrose preference test, forced swimming test, and balance beam test. Golgi and hematoxylin-eosin staining assessed neuronal repair, while quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and Western blotting evaluated effects on BDNF (brain-derived neurotrophic factor), hypothalamic-pituitary-adrenal axis factors, and the cAMP/PKA (protein kinase A)/CREB (cAMP-response element-binding protein) pathway. The study first determined the effects of different intensities of iTBS stimulation on neurological recovery in PSD rats. Second, the effects of iTBS stimulation on the cAMP/PKA/CREB pathway were verified using adenoviral blockade of PKA and CREB at iTBS-1800.
Results: PSD models showed decreased vertical movement, locomotor distance, and sucrose preference and increased immobility time and balance beam test score, which were reversed by iTBS. iTBS increased dendritic length and spine density in Purkinje cells, alleviated neuronal damage in multiple brain regions, and enhanced BDNF synthesis. It also regulated adrenocorticotropic hormone, cortisol, and GR (glucocorticoid receptor) expression, and activated the cAMP/PKA/CREB pathway.
Conclusions: Cerebellar iTBS improves PSD by activating the cAMP-PKA/CREB pathway, increasing BDNF, and reducing hypothalamic-pituitary-adrenal axis hyperactivity, suggesting potential for human PSD treatment.
期刊介绍：
Stroke is a monthly publication that collates reports of clinical and basic investigation of any aspect of the cerebral circulation and its diseases. The publication covers a wide range of disciplines including anesthesiology, critical care medicine, epidemiology, internal medicine, neurology, neuro-ophthalmology, neuropathology, neuropsychology, neurosurgery, nuclear medicine, nursing, radiology, rehabilitation, speech pathology, vascular physiology, and vascular surgery.
The audience of Stroke includes neurologists, basic scientists, cardiologists, vascular surgeons, internists, interventionalists, neurosurgeons, nurses, and physiatrists.
Stroke is indexed in Biological Abstracts, BIOSIS, CAB Abstracts, Chemical Abstracts, CINAHL, Current Contents, Embase, MEDLINE, and Science Citation Index Expanded.
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