What is the biological significance of BDNF mRNA targeting in the dendrites? Clues from epilepsy and cortical development.
The neurotrophin brain-derived neurotrophic factor (BDNF) is a regulatory factor of several, partially contrasting, aspects of the biology of neural cells, including survival, growth, differentiation, and cell death. Regulation of the local availability of BDNF at distinct subcellular domains such as the cell soma, dendrites, axons, and spines appears to be the key to conferring spatial and temporal specificity of the different effects elicited by this neurotrophin. This article reviews recent findings in the context of epileptogenesis and visual cortex maturation that showed that different BDNF messenger RNA (mRNA) transcripts are localized at different subcellular locations in hippocampal and cortical neurons. It also reviews findings demonstrating that strong depolarizing stimuli, both in vitro and in vivo, elicit accumulation of BDNF mRNA and protein in the distal dendrites through a signaling pathway involving the activation of the N-methyl-D-aspartate and tyrosine kinase B receptors and an intracellular increase in Ca2+ concentration. Finally, this article proposes that the regulation of the delivery of BDNF mRNA and protein to the different subcellular domains--particularly the dendritic compartment--may represent a fundamental aspect of the processes of cellular and synaptic morphological rearrangements underlying epileptogenesis and postnatal development of the visual cortex.
Tongiorgi
Enrico
E
BRAIN Centre for Neuroscience, Department of Biology, University of Trieste, Trieste, Italy. tongi@units.it
Domenici
Luciano
L
Simonato
Michele
M
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002451:Cell Compartmentation / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002540:Cerebral Cortex / Q000254:growth & development* / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism; D006801:Humans; D009473:Neuronal Plasticity / Q000235:genetics*; D021381:Protein Transport / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger