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The present work searched for the actions of QUIN in primary striatal neurons. Neurons exposed to 10 \u00b5M QUIN presented hyperphosphorylated neurofilament (NF) subunits (NFL, NFM, and NFH). Hyperphosphorylation was abrogated in the presence of protein kinase A and protein kinase C inhibitors H89 (20 \u03bcM) and staurosporine (10 nM), respectively, as well as by specific antagonists to N\u2010methyl\u2010D\u2010aspartate (50 \u00b5M DL\u2010AP5) and metabotropic glutamate receptor 1 (100 \u00b5M MPEP). Also, intra\u2010 and extracellular Ca<jats:sup>2+<\/jats:sup>chelators (10 \u00b5M BAPTA\u2010AM and 1 mM EGTA, respectively) and Ca<jats:sup>2+<\/jats:sup>influx through L\u2010type voltage\u2010dependent Ca<jats:sup>2+<\/jats:sup>channel (10 \u00b5M verapamil) are implicated in QUIN\u2010mediated effects. Cells immunostained for the neuronal markers \u03b2III\u2010tubulin and microtubule\u2010associated protein 2 showed altered neurite\/neuron ratios and neurite outgrowth. NF hyperphosphorylation and morphological alterations were totally prevented by conditioned medium from QUIN\u2010treated astrocytes. Cocultured astrocytes and neurons interacted with one another reciprocally, protecting them against QUIN injury. Cocultured cells preserved their cytoskeletal organization and cell morphology together with unaltered activity of the phosphorylating system associated with the cytoskeleton. This article describes cytoskeletal disruption as one of the most relevant actions of QUIN toxicity in striatal neurons in culture with soluble factors secreted by astrocytes, with neuron\u2013astrocyte interaction playing a role in neuroprotection. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jnr.23494","type":"journal-article","created":{"date-parts":[[2014,10,13]],"date-time":"2014-10-13T05:33:43Z","timestamp":1413178423000},"page":"268-284","source":"Crossref","is-referenced-by-count":36,"title":["Quinolinic acid induces disrupts cytoskeletal homeostasis in striatal neurons. 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