Chemokine (C-C motif) ligand 2 (CCL2), initially identified as monocyte chemoattractant protein-1 (MCP-1), recruits immune cells to the central nervous system (CNS) during autoimmune inflammation. CCL2 can be expressed by multiple cell types, but which cells are responsible for CCL2 function during acute and chronic phases of autoimmune disease is not known. We determined the role of CCL2 in astrocytes in vivo during experimental autoimmune encephalomyelitis (EAE) by using Cre-loxP gene deletion. Mice with a conditional gene deletion of CCL2 from astrocytes had less severe EAE late in disease while having a similar incidence and severity of disease at onset as compared to wild type (WT) control littermates. EAE mice devoid of CCL2 in astrocytes had less macrophage and T cell inflammation in the white matter of the spinal cord and less diffuse activation of astrocytes and microglia in both white and gray matter as well as less axonal loss and demyelination, compared to WT littermates. These findings demonstrate that CCL2 in astrocytes plays an important role in the continued recruitment of immune cells and activation of glial cells in the CNS during chronic EAE, thereby suggesting a novel cell specific target for neuroprotective treatments of chronic neuroinflammatory diseases.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4343306 | PMC |
http://dx.doi.org/10.1016/j.jneuroim.2014.06.009 | DOI Listing |
Epilepsia
November 2024
Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, University College London, London, UK.
Objective: Epilepsy involves significant changes in neural cells during epileptogenesis. Although the molecular mechanism of epileptogenesis remains obscure, changes in gene regulation play a crucial role in the evolution of epilepsy. This study aimed to compare changes in a subset of specific genes during epilepsy development, focusing on the period after the first spontaneous seizure, to identify critical time windows for targeting different regulators.
View Article and Find Full Text PDFBrain
October 2024
Department of Physiology and Pharmacology, Faculty of Medicine, Tel Aviv University, Tel Aviv, 6997801, Israel.
Over the last two decades, the diagnosis and treatment of breast cancer patients have considerably improved. However, brain metastases remain a major clinical challenge and a leading cause of mortality. Thus, a better understanding of the pathways involved in the metastatic cascade is essential.
View Article and Find Full Text PDFZhen Ci Yan Jiu
October 2024
Guangxi University of Chinese Medicine, Nanning 530001, China.
J Neuroimmune Pharmacol
October 2024
Laboratory of Neurobiology, Príncipe Felipe Research Centre, Valencia, 46012, Spain.
Neurobiol Dis
October 2024
Paul Flechsig Institute for Brain Research, University of Leipzig, 04103 Leipzig, Germany. Electronic address:
Dipeptidyl peptidase 4 (DPP4; CD26) is involved in the regulation of various metabolic, immunological, and neurobiological processes in healthy individuals. Observations based on epidemiological data indicate that DPP4 inhibition by gliptins, typically used in patients with diabetes, may reduce the risk for cerebral ischemia and may also improve related outcomes. However, as DPP4 inhibitor application is neither complete nor specific for suppression of DPP4 enzymatic activity and DPP4 has non-enzymatic functions as well, the variety of consequences is a matter of debate.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!