دورية أكاديمية
أعرض في EDS

Repeated Systemic Treatment with Rapamycin Affects Behavior and Amygdala Protein Expression in Rats.

التفاصيل البيبلوغرافية
العنوان: Repeated Systemic Treatment with Rapamycin Affects Behavior and Amygdala Protein Expression in Rats.
المؤلفون: Hadamitzky M; Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Herring A; Institute of Neuropathology, University Hospital Essen, Essen, Germany., Kirchhof J; Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Bendix I; Department of Pediatrics I/ Experimental perinatal Neuroscience, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Haight MJ; Department of Anesthesia, School of Medicine, University of San Francisco, San Francisco CA., Keyvani K; Institute of Neuropathology, University Hospital Essen, Essen, Germany., Lückemann L; Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Unteroberdörster M; Department of Neurosurgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Schedlowski M; Institute of Medical Psychology and Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.; Department of Clinical Neuroscience, Osher Center for Integrative Medicine, Karolinska Institutet, Stockholm, Sweden.
المصدر: The international journal of neuropsychopharmacology [Int J Neuropsychopharmacol] 2018 Jun 01; Vol. 21 (6), pp. 592-602.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 9815893 Publication Model: Print Cited Medium: Internet ISSN: 1469-5111 (Electronic) Linking ISSN: 14611457 NLM ISO Abbreviation: Int J Neuropsychopharmacol Subsets: MEDLINE
أسماء مطبوعة: Publication: 2015- : Oxford Oxford University Press
Original Publication: Cambridge, [England] : Cambridge University Press,
مواضيع طبية MeSH: Amygdala/*drug effects , Amygdala/*metabolism , Anxiety/*metabolism , Behavior, Animal/*drug effects , Immunosuppressive Agents/*pharmacology , Sirolimus/*pharmacology, Animals ; Anxiety/etiology ; Behavior, Animal/physiology ; Body Weight/drug effects ; Corticosterone/blood ; Dose-Response Relationship, Drug ; Exploratory Behavior/drug effects ; Exploratory Behavior/physiology ; Immunosuppressive Agents/adverse effects ; Male ; Maze Learning/drug effects ; Maze Learning/physiology ; Motor Activity/drug effects ; Motor Activity/physiology ; Proteome/drug effects ; Random Allocation ; Rats ; Receptors, Glucocorticoid/metabolism ; Sirolimus/adverse effects
مستخلص: Background: Clinical data indicate that therapy with small-molecule immunosuppressive drugs is frequently accompanied by an incidence rate of neuropsychiatric symptoms. In the current approach, we investigated in rats whether repeated administration of rapamycin, reflecting clinical conditions of patients undergoing therapy with this mammalian target of rapamycin inhibitor, precipitates changes in neurobehavioral functioning.
Methods: Male adult Dark Agouti rats were daily treated with i.p. injections of rapamycin (1, 3 mg/kg) or vehicle for 8 days. On days 6 and 7, respectively, behavioral performance in the Elevated Plus-Maze and the Open-Field Test was evaluated. One day later, amygdala tissue and blood samples were taken to analyze protein expression ex vivo.
Results: The results show that animals treated with rapamycin displayed alterations in Elevated Plus-Maze performance with more pronounced effects in the higher dose group. Besides, an increase in glucocorticoid receptor density in the amygdala was seen in both treatment groups even though p-p70 ribosomal S6 kinase alpha, a marker for mammalian target of rapamycin functioning, was not affected. Protein level of the neuronal activity marker c-Fos was again only elevated in the higher dose group. Importantly, effects occurred in the absence of acute peripheral neuroendocrine changes.
Conclusions: Our findings indicate that anxiety-related behavior following rapamycin treatment was not directly attributed to mTOR-dependent mechanisms or stress but rather due to hyperexcitability of the amygdala together with glucocorticoid receptor-regulated mechanism(s) in this brain region. Together, the present results support the contention that subchronic treatment with rapamycin may induce neurobehavioral alterations in healthy, naive subjects. We here provide novel insights in central effects of systemic rapamycin in otherwise healthy subjects but also raise the question whether therapy with this drug may have detrimental effects on patients' neuropsychological functioning during immune therapy.
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المشرفين على المادة: 0 (Immunosuppressive Agents)
0 (Proteome)
0 (Receptors, Glucocorticoid)
W36ZG6FT64 (Sirolimus)
W980KJ009P (Corticosterone)
تواريخ الأحداث: Date Created: 20180221 Date Completed: 20190708 Latest Revision: 20190708
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC6007742
DOI: 10.1093/ijnp/pyy017
PMID: 29462337
قاعدة البيانات: MEDLINE
الوصف
تدمد:1469-5111
DOI:10.1093/ijnp/pyy017