Cognitive disorders in mice: cytokine signaling pathways as therapeutic targets
| Autor: | Galina Shmarina, Alexander Pukhalsky, Vladimir Alioshkin |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Melphalan
Male Cyclophosphamide medicine.medical_treatment Pharmacology Biochemistry T-Lymphocytes Regulatory Mice Genetics medicine Animals Receptor Maze Learning Molecular Biology Antineoplastic Agents Alkylating Mice Inbred BALB C Behavior Animal business.industry NF-kappa B Cognition Receptors Interleukin-2 Original Articles NFKB1 Cytokine Molecular Medicine Cytokines Signal transduction business Cognition Disorders Homeostasis Immunosuppressive Agents Stress Psychological Biotechnology medicine.drug Signal Transduction |
| Zdroj: | Omics : a journal of integrative biology. 16(1-2) |
| ISSN: | 1557-8100 |
| Popis: | Surplus accumulation of regulatory T cells (Tregs) is known to be at the bottom of many morbid conditions, among them being neuropsychiatric diseases. In particular, Tregs may inhibit Th1 cells, including brain autoimmune lymphocytes, controlling the local microglial response and brain tissue homeostasis. The present study was undertaken in an attempt to suggest a novel approach for the treatment of maladaptation to mental stress associated with excessive Treg accumulation. Recently it was shown that alkylating drugs (ADs), such as melphalan and cyclophosphamide (Cy) in the dose 100-fold lower than cytostatic one are capable to disturb signal transduction by IL-2R. In this study we demonstrated that IL-2R is not a unique receptor, which may be blocked with ADs. Similar effect has been shown for two other surface receptors: TNFR and Fas. Molecular mechanisms of the receptor blockage were investigated on the model of TNF signaling. Study of NF-κB activity in nuclear extracts showed that alkylating agents act at the level of surface receptor or of the receptor platform. It was also shown that ADs administration in ultralow doses results in selective elimination of Tregs. In this study we used a new laboratory model of Treg accumulation in mice. Such Treg accumulation was associated with cognitive and behavioral abnormalities, which may be prevented by Cy administration. |
| Databáze: | OpenAIRE |
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