Cocaine induces the expression of homer 1b/c, homer 3a/b, and hsp 27 proteins in rat cerebellum.
The long homer proteins 1b/c, 2a/b, and 3a/b play an important role in postsynaptic neurons by clustering glutamate receptors and by coupling the receptors with various intracellular effectors. Using immunohistochemistry and Western-blot analysis, this study shows that the expression of the long homer isoforms 1b/c and 3a/b was induced in rat cerebellum in response to cocaine administration. Acute treatment produced a very robust induction of both constitutive isoforms, whereas repeated treatment for 10 days induced a large expression of homer 1b/c and a more modest increase in the expression of the 3a/b isoform. The heat shock protein hsp 27 was also considerably induced in the cerebellum of cocaine-treated rats, suggesting that it participates in assisting the correct folding of proteins, and by counteracting oxidative stress mechanisms triggered by the psychostimulant. In addition of being expressed in Purkinje neurons, homer 3a/b and hsp 27, but not homer 1b/c, were localized within Bergmann glial cells and in their extensions, which surround Purkinje cells, as assessed by coimmunoreactivity with glial fibrillary acidic protein. Cocaine was also found to induce both proteins in the Bergmann glial cells. Since we found that homer 3a/b colocalized with the mGluR1 receptor in Purkinje cells, the data suggest that the long homer isoforms are involved in the cocaine-induced neuroplasticity that takes place in the cerebellum, by reshaping postsynaptic densities in Purkinje cell dendrites.
Dietrich
Jean-Bernard
JB
Inserm, U575, Centre de Neurochimie, 5 rue Blaise Pascal, 67084 Strasbourg Cedex, France.
Arpin-Bott
Marie-Pierre
MP
Kao
Dany
D
Dirrig-Grosch
Sylvie
S
Aunis
Dominique
D
Zwiller
Jean
J
D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D000072233:Homer Scaffolding Proteins; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D018613:Microscopy, Confocal; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000187:drug effects*; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism; D000099190:MAP-Kinase-Activated Kinase 2
D002352:Carrier Proteins; D003042:Cocaine; D018765:Dopamine Uptake Inhibitors; D000072233:Homer Scaffolding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases; D018094:Receptors, Metabotropic Glutamate; D000099190:MAP-Kinase-Activated Kinase 2; C104077:metabotropic glutamate receptor type 1