Astrocytes Protect The CNS: Antigen-Specific T-Helper Cell Responses Are Inhibited By Astrocyte-Induced Upregulation Of CTLA-4 (CD152)
Gimsa U, ORen A, Pandiyan P, Teichmann D, Bechmann I, Nitsch R, Brunner-Weinzierl MC
J Mol Med 2004 Jun;82(6):364-72
University of Rostock, Department of Neurology, Gehlsheimer Strasse 20, 18147, Rostock, Germany, ulrike
Astrocytes are the first cells that are encountered by T-Cells invading the Central Nervous System (CNS) by crossing the Blood-Brain Barrier.
We show that primary Astrocytes contribute to the Immune privilege of the CNS by suppressing Th1 and Th2 Cell activation, proliferation and effector function.
Moreover, this Astrocyte-mediated inhibition of Th Effector Cells was effective on already activated, proliferating cells. Transforming Growth Factor-beta (TGF-ß) secreted by Astrocytes or T-Cells was not the major factor in the inhibition.
The inhibition of T-Cell proliferation induced by Astrocytes was mainly mediated by upregulation of CTLA-4 on already activated T-Cells, which occurred both with and without cell-cell contact.
Upregulation of the inhibitory molecule CTLA-4 on AutoReactive Th Cells, as mediated by Astrocytes, thus represents a novel mechanism for securing the Immune privilege of the CNS.
Astrocytic AdrenoCeptors: A Major Drug Target In Neurological And Psychiatric Disorders?
Hertz L, Chen Y, Gibbs ME, Zang P, Peng L
Curr Drug Targets CNS Neurol Disord 2004 Jun;3(3):239-67
China Medical University, College of Basic Medical Sciences, Shenyang 110001, P.R. China
Considerable attention has recently been paid to Astrocyte functions, which are briefly summarized.
A large amount of data is available about AdrenoCeptor expression and function in Astrocytes, some of it dating back to the 1970's and some of it very recent.
This material is reviewed in the present paper. The Brain is innervated by NorAdrenergic fibers extending from Locus Coeruleus in the BrainStem, which in turn is connected to a network of Adrenergic and NorAdrenergic Nuclei in the Medulla and Pons.
Contributing to the control of NorAdrenergic, Serotonergic, Dopaminergic and Cholinergic function, both in the Central Nervous System (CNS) and in the Periphery.
In the CNS Astrocytes constitute a major target for NorAdrenergic innervation, which regulates Morphological plasticity, energy metabolism, membrane transport, Gap Junction permeability and Immunological Responses in these cells.
NorAdrenergic effects on Astrocytes are essential during consolidation of episodic, long-term memory, which is reinforced by beta-Adrenergic activation.
GlycoGenolysis and synthesis of Glutamate and Glutamine from Glucose, both of which are metabolic processes restricted to Astrocytes, occur at several time-specific stages during the consolidation.
Astrocytic abnormalities are almost certainly important in the pathogenesis of Multiple Sclerosis and in all probability contribute essentially to inflammation and malfunction in Alzheimer's Disease and to mood disturbances in Affective Disorders.
NorAdrenergic function in Astrocytes is severely disturbed by chronic exposure to Cocaine, which also changes Astrocyte morphology.
Development of drugs modifying NorAdrenergic Receptor activity and/or down-stream signaling is advocated for treatment of several Neurological/Psychiatric Disorders and for NeuroProtection.
Astrocytic preparations are suggested for study of mechanism(s) of action of AntiDepressant drugs and PathoPhysiology of Mood Disorders.
Chemokines And Glial Cells: A Complex Network In The Central Nervous System
Ambrosini E, Aloisi F
NeuroChem Res 2004 May;29(5):1017-38
Istituto Superiore di Sanita, Department of Cell Biology and NeuroScience, Viale Regina Elena 299, 00161 Rome, Italy
Chemokines are small secreted proteins that are essential for the recruitment and activation of specific Leukocyte subsets at sites of inflammation and for the development and Homeostasis of Lymphoid and NonLymphoid tissues.
During the past decade, Chemokines and their Receptors have also emerged as key signaling molecules in NeuroInflammatory Processes and in the development and functioning of the Central Nervous System.
Neurons and Glial Cells, including Astrocytes, Oligodendrocytes, and Microglia Cells, have been identified as cellular sources and/or targets of Chemokines produced in the Central Nervous System in physiological and pathological conditions.
In this article, we provide an update of Chemokines and Chemokine Receptors expressed by Glial Cells focusing on their biological functions and implications in Neurological Diseases.
Production Of NeuroProtective NGF In Astrocyte T-Helper Cell Cocultures Is Upregulated Following Antigen Recognition
Oren A, Falk K, Rotzschke O, Bechmann I, Nitsch R, Gimsa U
J NeuroImmunol 2004 Apr;149(1-2):59-65
Max Delbruck Center for Molecular Medicine, Robert-Rossle-Strasse 10, Berlin D-13125, Germany
Astrocytic production of Nerve Growth Factor (NGF) is increased during inflammation of the Central Nervous System (CNS).
Here we show that cell-cell interaction between primary murine Astrocytes and Myelin Basic Protein (MBP)-specific T-Cell Receptor (TCR) transgenic Th1 and Th2 Cells significantly increased production of NGF.
This upregulation was found to be dependent on Antigen recognition. Neutralization of Cytokines produced in cocultures did not affect NGF production. This novel finding suggests a NeuroProtective role of Astrocytes during T-Cell-mediated inflammation in the CNS.