Dendritic targeting of mRNAs for plasticity genes in experimental models of temporal lobe epilepsy.
OBJECTIVE
To analyze whether the subcellular localization of the messenger RNAs (mRNAs) coding for the neurotrophin brain-derived neurotrophic factor (BDNF), its receptor TrkB, and the alpha and beta subunits of calcium-calmodulin-dependent kinase II (CaMKII) are modified after pilocarpine and kindled seizures.


METHODS
Epilepsy models: pilocarpine and kindling. Analysis of mRNA levels in the dendrites: high-resolution, nonradioactive in situ hybridization.


RESULTS
Nonstimulated rats: BDNF, TrkB, and CaMKII-beta mRNAs localized in the soma and in the proximal dendrites of hippocampal pyramidal cells, and in the soma only of dentate gyrus (DG) granule cells; CaMKII-alpha mRNA localized throughout the dendritic length in neurons of all hippocampal subfields. Pilocarpine seizures: increased staining levels of CaMKII-alpha mRNA throughout the whole dendritic length in all hippocampal subfields; induction of CaMKII-beta, BDNF, and TrkB mRNAs dendritic targeting in CA1, CA3, and DG neurons. Class 2 kindled seizures: increase in dendritic staining intensity for CaMKII-alpha in CA1, CA3, and DG neurons; induction of dendritic localization of CaMKII-beta, BDNF, and TrkB mRNAs in CA3 neurons. Fully kindled seizures: no change in the subcellular distribution of BDNF, TrkB and CaMKII-beta mRNAs; reduction of CaMKII-alpha mRNA dendritic staining, as compared with unstimulated kindled animals.


CONCLUSIONS
Data provide evidence that BDNF, TrkB, and CaMKII-alpha and -beta mRNAs are accumulated in the dendrites of specific hippocampal neurons during pilocarpine seizures and kindling development. The dendritic targeting of these genes may be causally involved in epileptogenesis and thus may represent a new therapeutic target for some forms of partial epilepsy.
Department of Experimental and Clinical Medicine, Section of Pharmacology, University of Ferrara, via Fossato di Mortara 17-19, 44100 Ferrara, Italy. m.simonato@unife.it
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M
Simonato
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Bregola
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Armellin
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Del Piccolo
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Rodi
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Zucchini
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Tongiorgi
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D003292:Convulsants; D003712:Dendrites / Q000502:physiology*; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000235:genetics* / Q000378:metabolism*; D018390:Gene Targeting; D007696:Kindling, Neurologic; D008297:Male; D009473:Neuronal Plasticity / Q000235:genetics*; D010862:Pilocarpine; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D012016:Reference Values; D012640:Seizures / Q000139:chemically induced / Q000209:etiology; D013347:Subcellular Fractions / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D003292:Convulsants; D020033:Protein Isoforms; D012333:RNA, Messenger; D010862:Pilocarpine; D020813:Receptor, trkB; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases