Endocytosis and autophagy in cerebral ischemia and excitotoxicity

Vaslin, Anne; Puyal, Julien; Waechter, Vanessa; Borsello, Tiziana; Clarke, Peter G. H.

doi:10.1038/sj.jcbfm.9591524.0461

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“…The fact that excitotoxic treatment leads to enhanced endocytosis before the onset of cell death suggests that it may serve as a means for targeting drugs into excitotoxically stressed neurons before they die. We are currently exploring this, and have preliminary evidence that an equivalent endocytic phenomenon occurs in a clinically relevant model of cerebral ischemia (Vaslin et al . 2005).…”

Section: Discussionmentioning

confidence: 99%

Excitotoxicity‐related endocytosis in cortical neurons

Vaslin

Puyal

Borsello

et al. 2007

Journal of Neurochemistry

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Recent studies showed that endocytosis is enhanced in neurons exposed to an excitototoxic stimulus. We here confirm and analyze this new phenomenon using dissociated cortical neuronal cultures. NMDA-induced uptake (FITC-dextran or FITC or horseradish peroxidase) occurs in these cultures and is due to endocytosis, not to cell entry through damaged membranes; it requires an excitotoxic dose of NMDA and is dependent on extracellular calcium, but occurs early, while the neuron is still intact and viable. It involves two components, NMDA-induced and constitutive, with different characteristics. Neither component involves specific binding of the endocytosed molecules to a saturable receptor. Strikingly, molecules internalized by the NMDA-induced component are targeted to neuronal nuclei. This component, but not the constitutive one, is blocked by a c-Jun N-terminal protein kinase inhibitor. In conclusion, an excitotoxic dose of NMDA triggers c-Jun N-terminal protein kinase-dependent endocytosis in cortical neuronal cultures, providing an in vitro model of the excitotoxicity-induced endocytosis reported in intact tissues.

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Section: Discussionmentioning

confidence: 99%