Systemic immunization with altered myelin basic protein peptide produces sustained antidepressant-like effects
Autor: | Ying Han, Ling-Zhi Xu, Shi-Qiu Meng, Lin Lu, Yan-Xue Xue, Wei Yan, Jiahui Deng, Jia-Li Li, Jie Shi, Cheng-Yu Sun, Kai Yuan, Wei-Li Zhu, Serik Tabarak, Lu Cao |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Central nervous system Proinflammatory cytokine 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Neurotrophic factors Internal medicine medicine Cyclic adenosine monophosphate Chronic stress Molecular Biology Microglia biology business.industry Myelin basic protein Psychiatry and Mental health 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry biology.protein business 030217 neurology & neurosurgery Behavioural despair test |
Zdroj: | Molecular Psychiatry. 25:1260-1274 |
ISSN: | 1476-5578 1359-4184 |
Popis: | Immune dysregulation, specifically of inflammatory processes, has been linked to behavioral symptoms of depression in both human and rodent studies. Here, we evaluated the antidepressant effects of immunization with altered peptide ligands of myelin basic protein (MBP)-MBP87-99[A91, A96], MBP87-99[A91], and MBP87-99[R91, A96]-in different models of depression and examined the mechanism by which these peptides protect against stress-induced depression. We found that a single dose of subcutaneously administered MBP87-99[A91, A96] produced antidepressant-like effects by decreasing immobility in the forced swim test and by reducing the escape latency and escape failures in the learned helplessness paradigm. Moreover, immunization with MBP87-99[A91, A96] prevented and reversed depressive-like and anxiety-like behaviors that were induced by chronic unpredictable stress (CUS). However, MBP87-99[R91, A96] tended to aggravate CUS-induced anxiety-like behavior. Chronic stress increased the production of peripheral and central proinflammatory cytokines and induced the activation of microglia in the prelimbic cortex (PrL), which was blocked by MBP87-99[A91, A96]. Immunization with MBP-derived altered peptide ligands also rescued chronic stress-induced deficits in p11, phosphorylated cyclic adenosine monophosphate response element binding protein, and brain-derived neurotrophic factor expression. Moreover, microinjections of recombinant proinflammatory cytokines and the knockdown of p11 in the PrL blunted the antidepressant-like behavioral response to MBP87-99[A91, A96]. Altogether, these findings indicate that immunization with altered MBP peptide produces prolonged antidepressant-like effects in rats, and the behavioral response is mediated by inflammatory factors (particularly interleukin-6), and p11 signaling in the PrL. Immune-neural interactions may impact central nervous system function and alter an individual's response to stress. |
Databáze: | OpenAIRE |
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