Activation of Group II/III metabotropic glutamate receptors attenuates LPS-induced astroglial neurotoxicity via promoting glutamate uptake. 2006

Fang Zhou, and Hong-Hong Yao, and Jia-Yong Wu, and Yan-Jing Yang, and Jian-Hua Ding, and Ji Zhang, and Gang Hu
Laboratory of Neuropharmacology, Department of Anatomy, Histology and Pharmacology, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.

Altered glial function that leads to oxidative stress and excitotoxicity may contribute to the initiation or progression of neuronal death in neurodegenerative diseases. We report the pivotal role of astroglial Group II and III metabotropic glutamate receptors (mGluR) against neurotoxicity. Activation of Group II or III mGluR on astrocytes with selective agonists DCG-IV or L-AP4 respectively inhibited astroglial lipopolysaccharide (LPS)-conditioned medium induced apoptosis of primary cultured mesencephalic neurons. Specific Group II or III mGluR antagonists APICA or MSOP completely abolished the neuroprotective effects of DCG-IV and L-AP4. Morphologic analysis showed that DCG-IV or L-AP4 could also attenuate the astroglial neurotoxicity to dopaminergic neurons. Measurement of extracellular glutamate concentration and [(3)H]-glutamate uptake showed that the restoration of glutamate uptake capability in LPS-treated astrocytes might be involved in the neuroprotective effects of activating astroglial Group II or III mGluR. Furthermore, we found that the repression of astroglial uptake function could be revived by GSH, and both Group II and III mGluR agonists could recover the endogenous reduced glutathione (GSH) level in LPS-treated astrocytes. These results suggested that the possible mechanisms of neuroprotection by either Type II or Type III mGluR activation may involve restoration of endogenous GSH, in turn affording recovery of astroglial capability to take up glutamate.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010768 Phosphoserine The phosphoric acid ester of serine. Serine Phosphate,Phosphorylserine,Seryl Phosphate,Phosphate, Serine,Phosphate, Seryl
D011422 Propionates Derivatives of propionic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxyethane structure. Propanoate,Propanoic Acid,Propionate,Propanoates,Propanoic Acid Derivatives,Propanoic Acids,Propionic Acid Derivatives,Propionic Acids,Acid, Propanoic,Acids, Propanoic,Acids, Propionic,Derivatives, Propanoic Acid,Derivatives, Propionic Acid
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003521 Cyclopropanes Three-carbon cycloparaffin cyclopropane (the structural formula (CH2)3) and its derivatives.
D005978 Glutathione A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides. Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D005998 Glycine A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. Aminoacetic Acid,Glycine, Monopotassium Salt,Glycine Carbonate (1:1), Monosodium Salt,Glycine Carbonate (2:1), Monolithium Salt,Glycine Carbonate (2:1), Monopotassium Salt,Glycine Carbonate (2:1), Monosodium Salt,Glycine Hydrochloride,Glycine Hydrochloride (2:1),Glycine Phosphate,Glycine Phosphate (1:1),Glycine Sulfate (3:1),Glycine, Calcium Salt,Glycine, Calcium Salt (2:1),Glycine, Cobalt Salt,Glycine, Copper Salt,Glycine, Monoammonium Salt,Glycine, Monosodium Salt,Glycine, Sodium Hydrogen Carbonate,Acid, Aminoacetic,Calcium Salt Glycine,Cobalt Salt Glycine,Copper Salt Glycine,Hydrochloride, Glycine,Monoammonium Salt Glycine,Monopotassium Salt Glycine,Monosodium Salt Glycine,Phosphate, Glycine,Salt Glycine, Monoammonium,Salt Glycine, Monopotassium,Salt Glycine, Monosodium

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