کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4324896 | 1613945 | 2013 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Amphetamine increases phosphorylation of MAPK/ERK at synaptic sites in the rat striatum and medial prefrontal cortex Amphetamine increases phosphorylation of MAPK/ERK at synaptic sites in the rat striatum and medial prefrontal cortex](/preview/png/4324896.png)
Mitogen-activated protein kinases (MAPKs) play a central role in cell signaling. Extracellular signal-regulated kinase (ERK) is a prototypic subclass of MAPKs and is densely expressed in postmitotic neurons of adult mammalian brains. Active ERK translocates into the nucleus to regulate gene expression. Additionally, ERK is visualized in neuronal peripheries, such as distal synaptic structures. While nuclear ERK is a known sensitive target of psychostimulants, little is known about the responsiveness of synaptic ERK to stimulants. In this study, we focused on ERK at synaptic versus extrasynaptic sites and investigated its responses to the psychostimulant amphetamine in the adult rat striatum and medial prefrontal cortex (mPFC) in vivo. We used a pre-validated biochemical fractionation procedure to isolate synapse- and extrasynapse-enriched membranes. We found that two common ERK isoforms (ERK1 and ERK2) were concentrated more in extrasynaptic fractions than in synaptic fractions in striatal and cortical neurons under normal conditions. At synaptic sites, ERK2 was noticeably more abundant than ERK1. Acute injection of amphetamine induced an increase in ERK2 phosphorylation in the synaptic fraction of striatal neurons, while the drug did not alter extrasynaptic ERK2 phosphorylation. Similar results were observed in the mPFC. In both synaptic and extrasynaptic compartments, total ERK1/2 proteins remained stable in response to amphetamine. Our data establish the subsynaptic distribution pattern of MAPK/ERK in striatal and cortical neurons. Moreover, the synaptic pool of ERK2 in these neurons can be selectively activated by amphetamine.
► ERK2 is present at synaptic sites in the rat striatum and prefrontal cortex.
► Acute amphetamine increased ERK2 phosphorylation in the striatum.
► Amphetamine also increased ERK2 phosphorylation in the medial prefrontal cortex.
Journal: Brain Research - Volume 1494, 4 February 2013, Pages 101–108