Stimulation of excitatory amino acid release from adult mouse brain glia subcellular particles by high mobility group box 1 protein

• Published in: Journal of neurochemistry 2006-11, Vol.99 (3), p.827-838
• Main Authors: Pedrazzi, Marco, Raiteri, Luca, Bonanno, Giambattista, Patrone, Mauro, Ledda, Sabina, Passalacqua, Mario, Milanese, Marco, Melloni, Edon, Raiteri, Maurizio, Pontremoli, Sandro, Sparatore, Bianca
• Format: Article
• Language: English
• Subjects: Adults; Amino acids; Animals; Biological and medical sciences; Blotting, Western; Brain; Brain Chemistry - drug effects; Calcium - physiology; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Cerebellum - drug effects; Cerebellum - metabolism; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Cytokines; Detergents - pharmacology; Excitatory Amino Acid Transporter 1 - metabolism; Excitatory Amino Acids - metabolism; Fundamental and applied biological sciences. Psychology; glial glutamate‐aspartate transporter; gliosomes; glutamate release; Glutamic Acid - metabolism; high mobility group box 1; Hippocampus - drug effects; Hippocampus - metabolism; HMGB1 Protein - pharmacology; Male; Mice; Microscopy, Confocal; Neuroglia - drug effects; Neuroglia - metabolism; Neurosciences; Neurotransmitters; Presynaptic Terminals - drug effects; Presynaptic Terminals - metabolism; Proteins; Receptor for Advanced Glycation End Products; Receptors, Immunologic - metabolism; Rodents; Stimulation, Chemical; Subcellular Fractions - drug effects; Subcellular Fractions - metabolism; synaptosomes; Synaptosomes - drug effects; Synaptosomes - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2006.04120.x

The multifunctional protein high mobility group box 1 (HMGB1) is expressed in hippocampus and cerebellum of adult mouse brain. Our aim was to determine whether HMGB1 affects glutamatergic transmission by monitoring neurotransmitter release from glial (gliosomes) and neuronal (synaptosomes) re‐sealed subcellular particles isolated from cerebellum and hippocampus. HMGB1 induced release of the glutamate analogue [3H]d‐aspartate form gliosomes in a concentration‐dependent manner, whereas nerve terminals were insensitive to the protein. The HMGB1‐evoked release of [3H]d‐aspartate was independent of modifications of cytosolic Ca2+ , but it was blocked by dl‐threo‐β‐benzyloxyaspartate (dl‐TBOA), an inhibitor of glutamate transporters. HMGB1 also stimulated the release of endogenous glutamate in a Ca2+‐independent and dl‐TBOA‐sensitive manner. These findings suggest the involvement of carrier‐mediated release. Moreover, dihydrokainic acid, a selective inhibitor of glutamate transporter 1 (GLT1), does not block the effect of HMGB1, indicating a role for the glial glutamate‐aspartate transporter (GLAST) subtype in this response. We also demonstrate that HMGB1/glial particles association is promoted by Ca2+. Furthermore, although HMGB1 can physically interact with GLAST and the receptor for advanced glycation end products (RAGE), only its binding with RAGE is promoted by Ca2+. These results suggest that the HMGB1 cytokine could act as a modulator of glutamate homeostasis in adult mammal brain.