Differential effects on glial activation by a direct versus an indirect thrombin inhibitor
| Autor: | Annie Situ, Douglas L. Feinstein, Ana Lis Moyano, Paul E. Polak, Sergey Kalinin, Maria I. Givogri, David Braun, M. Natalia Marangoni |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Immunology Mice Transgenic Pharmacology Dabigatran 03 medical and health sciences Amyloid beta-Protein Precursor Mice 0302 clinical medicine Thrombin Alzheimer Disease Glial Fibrillary Acidic Protein Presenilin-1 Immunology and Allergy Medicine Animals Humans Neuroinflammation Amyloid beta-Peptides Microglia business.industry Calcium-Binding Proteins Microfilament Proteins Anticoagulants Brain Peptide Fragments Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Neurology Coagulation Gene Expression Regulation Direct thrombin inhibitor Mutation Female Neurology (clinical) Warfarin business Neuroglia 030217 neurology & neurosurgery medicine.drug Astrocyte Discovery and development of direct thrombin inhibitors |
| Zdroj: | Journal of neuroimmunology. 297 |
| ISSN: | 1872-8421 |
| Popis: | Thrombin is a potent regulator of brain function in health and disease, modulating glial activation and brain inflammation. Thrombin inhibitors, several of which are in clinical use as anti-coagulants, can reduce thrombin-dependent neuroinflammation in pathological conditions. However, their effects in a healthy CNS are largely unknown. In adult healthy mice, we compared the effects of treatment by the direct thrombin inhibitor dabigatran etexilate (DE), to those of warfarin, which acts by preventing vitamin K recycling essential for coagulation. After 4 weeks, warfarin increased both astrocyte GFAP and microglia Iba-1 staining throughout the CNS; whereas DE reduced expression of both markers. Warfarin, but not DE, reduced sulfatide levels; and warfarin showed longer lasting changes in cerebellar gene expression. DE also reduced glial activation in a mouse model of Alzheimer's disease, although no changes in amyloid plaque burden were observed. These results suggest that treatment with direct thrombin inhibitors may be preferable to those agents which reduce vitamin K levels and have the potential to increase glial activation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect