BDNF mRNA splice variants display activity-dependent targeting to distinct hippocampal laminae.
Brain-derived neurotrophic factor (BDNF) may exert contrasting effects depending on its different subcellular sites of action (soma, dendrites, axons). These contrasting effects may explain contradictory findings, for example that BDNF may favour or oppose epileptogenesis. We determined the distribution of five BDNF splice variants in the soma and dendrites of rat hippocampal principal neurons, after application of stimuli that prompt BDNF mRNA accumulation in dendrites (epileptogenic seizures). Under basal conditions, no BDNF mRNA splice variant was detectable in dendrites, while specific splice variants were found in dendrites in response to epileptogenic seizures. Three hours after pilocarpine administration, exon VI and exon II splice variants were found in dendrites, while exons I and IV transcripts displayed a strictly somatic localization. Three hours after kainate administration, only exon VI was found in dendrites. These data suggest that the regulated expression of different splice variants may provide a spatial code to ensure the delivery of BDNF to precise destinations in the cell soma or along the dendrites.
Chiaruttini
C
C
BRAIN Centre for Neuroscience, Department of Biology, University of Trieste, 34127 Trieste, Italy.
Sonego
M
M
Baj
G
G
Simonato
M
M
Tongiorgi
E
E
D017398:Alternative Splicing / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D003712:Dendrites; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology; D005091:Exons / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology*; D017403:In Situ Hybridization; D007608:Kainic Acid; D008297:Male; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D010862:Pilocarpine; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D010862:Pilocarpine; D007608:Kainic Acid