Spontaneous activity is an essential attribute of neuronal networks and plays a critical role in their development and maintenance.Upon blockade of activity with tetrodotoxin (TTX), neurons degenerate slowly and die in a manner resembling neurodegenerative diseases-induced neuronal cell death.The molecular cascade leading to this type of slow cell death is not entirely clear.
Primary post-natal cortical neurons were exposed to 15-eg2373cl TTX for up to two weeks, followed by molecular, biochemical and immunefluorescence analysis.The expression of the neuronal marker, neuron specific enolase (NSE), was down-regulated, as expected, but surprisingly, there was a concomitant and striking elevation in expression of tissue-type plasminogen activator (tPA).Immunofluorescence analysis indicated that tPA was highly elevated inside affected neurons.
Transfection of an endogenous tPA inhibitor, plasminogen activator inhibitor-1 color touch 7/97 (PAI-1), protected the TTX-exposed neurons from dying.These results indicate that tPA is a pivotal player in slowly progressing activity deprivation-induced neurodegeneration.