title: Activity-dependent dendritic targeting of BDNF and TrkB mRNAs in hippocampal neurons.
abstract: The mechanisms underlying the subcellular localization of neurotrophins and their receptors are poorly understood. We show that in cultured hippocampal neurons, the mRNAs for BDNF and TrkB have a somatodendritic localization, and we quantify the extent of their dendritic mRNA localization. In the dendrites the labeling covers on average the proximal 30% of the total dendritic length. On high potassium depolarization, the labeling of BDNF and TrkB mRNA extends on average to 68% of the dendritic length. This increase does not depend on new RNA synthesis, is inhibited by the Na+ channel blocker tetrodotoxin, and involves the activation of glutamate receptors. Extracellular Ca2+, partly flowing through L-type Ca2+ channels, is absolutely required for this process to occur. At the protein level, a brief stimulation of hippocampal neurons with 10 mM KCl leads to a marked increase of BDNF and TrkB immunofluorescence density in the distal portion of dendrites, which also occurs, even if at lower levels, when transport is inhibited by nocodazole. The protein synthesis inhibitor cycloheximide abolishes this increase. The activity-dependent modulation of mRNA targeting and protein accumulation in the dendrites may provide a mechanism for achieving a selective local regulation of the activity of neurotrophins and their receptors, close to their sites of action.
authors.affiliation: International School for Advanced Studies (SISSA), Neuroscience Program, 34014 Trieste, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Tongiorgi
authors.forename: M
authors.initials: M
authors.lastname: Righi
authors.forename: A
authors.initials: A
authors.lastname: Cattaneo
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000906:Antibodies; D000970:Antineoplastic Agents / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003712:Dendrites / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology; D007736:Kynurenic Acid / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D009543:Nifedipine / Q000494:pharmacology; D015739:Nocodazole / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D019208:Brain-Derived Neurotrophic Factor; D002121:Calcium Channel Blockers; D018691:Excitatory Amino Acid Antagonists; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D013779:Tetrodotoxin; D011189:Potassium Chloride; D003513:Cycloheximide; D020794:Receptor Protein-Tyrosine Kinases; D007736:Kynurenic Acid; D009543:Nifedipine; D015739:Nocodazole; D002118:Calcium