Brain-derived neurotrophic factor mRNA and protein are targeted to discrete dendritic laminas by events that trigger epileptogenesis.
Dendritic targeting of mRNA and local protein synthesis are mechanisms that enable neurons to deliver proteins to specific postsynaptic sites. Here, we demonstrate that epileptogenic stimuli induce a dramatic accumulation of BDNF mRNA and protein in the dendrites of hippocampal neurons in vivo. BDNF mRNA and protein accumulate in dendrites in all hippocampal subfields after pilocarpine seizures and in selected subfields after other epileptogenic stimuli (kainate and kindling). BDNF accumulates selectively in discrete dendritic laminas, suggesting targeting to synapses that are active during seizures. Dendritic targeting of BDNF mRNA occurs during the time when the cellular changes that underlie epilepsy are occurring and is not seen after intense stimuli that are non-epileptogenic, including electroconvulsive seizures and high-frequency stimulation. MK801, an NMDA receptor antagonist that can prevent epileptogenesis but not acute seizures, prevents the dendritic accumulation of BDNF mRNA, indicating that dendritic targeting is mediated via NMDA receptor activation. Together, these results suggest that dendritic accumulation of BDNF mRNA and protein plays a critical role in the cellular changes leading to epilepsy.
BRAIN Centre for Neuroscience, Department of Biology, University of Trieste, 34127 Trieste, Italy. tongi@units.it
Enrico
E
Tongiorgi
Mara
M
Armellin
Piero Giulio
PG
Giulianini
Gianni
G
Bregola
Silvia
S
Zucchini
Beatrice
B
Paradiso
Oswald
O
Steward
Antonino
A
Cattaneo
Michele
M
Simonato
D000818:Animals; D001692:Biological Transport; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002451:Cell Compartmentation; D003292:Convulsants / Q000633:toxicity; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004597:Electroshock; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D007608:Kainic Acid / Q000633:toxicity; D007696:Kindling, Neurologic; D008297:Male; D010862:Pilocarpine / Q000633:toxicity; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D013569:Synapses / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D003292:Convulsants; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D010862:Pilocarpine; D016291:Dizocilpine Maleate; D007608:Kainic Acid