Cocaine induces the expression of homer 1b/c, homer 3a/b, and hsp 27 proteins in rat cerebellum

Abstract

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.

Large-Scale, Ion-Current-Based Proteomic Investigation of the Rat Striatal Proteome in a Model of Short- and Long-Term Cocaine Withdrawal

“…According to literature reports, chronic cocaine administration compromises normal dopamine transporter (DAT) functions, thus posing oxidative stress on CNS and leading to elevated HSP expression 48 . This has been observed in several mammalian CNS regions, including hippocampus 48 , prefrontal cortex 49 and cerebellum 50 , and our results suggest that elevation of HSP expression also occurred in the striatum. Second, proteins involved in synaptic neurotransmission (e.g.…”

Sex differences in decreased limbic and cortical grey matter volume in cocaine dependence: a voxel‐based morphometric study

“…), and neuroadaptations have been found in rats administered cocaine (Dietrich et al . ). However, the significance to cocaine dependence of smaller versus larger cerebellar volume is unclear.…”

Homers regulate drug-induced neuroplasticity: Implications for addiction

“…In contrast to Homer1 and Homer2 gene products, Homer3 isoforms are localized primarily to hippocampus and cerebellum [105,106]. While both acute and repeated cocaine elevates cerebellar Homer3a/b expression [239], Homer3 KO mice do not exhibit a cocaine "presensitized" behavioral phenotype [34]. While transgenic mice over-expressing Homer1a within striatal striosome patches exhibit increased locomotor sensitivity in response to an acute challenge injection of amphetamine [240], AAV-mediated over-expression of Homer1a within the NAC or PFC does not alter the acute or the sensitized locomotor response to cocaine [35,173].…”