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Dendritic Targeting of mRNAs for Plasticity Genes in Experimental Models of Temporal Lobe Epilepsy
Author(s) -
Simonato M.,
Bregola G.,
Armellin M.,
Del Piccolo P.,
Rodi D.,
Zucchini S.,
Tongiorgi E.
Publication year - 2002
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1046/j.1528-1157.43.s.5.32.x
Subject(s) - tropomyosin receptor kinase b , hippocampal formation , epileptogenesis , neuroscience , dentate gyrus , brain derived neurotrophic factor , interneuron , dendritic spine , biology , neurotrophic factors , microbiology and biotechnology , chemistry , receptor , inhibitory postsynaptic potential , biochemistry
Summary: Purpose: 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 α and β 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‐β 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‐α mRNA localized throughout the dendritic length in neurons of all hippocampal subfields. Pilocarpine seizures: increased staining levels of CaMKII‐α mRNA throughout the whole dendritic length in all hippocampal subfields; induction of CaMKII‐β, BDNF, and TrkB mRNAs dendritic targeting in CA1, CA3, and DG neurons. Class 2 kindled seizures: increase in dendritic staining intensity for CaMKII‐α in CA1, CA3, and DG neurons; induction of dendritic localization of CaMKII‐β, BDNF, and TrkB mRNAs in CA3 neurons. Fully kindled seizures: no change in the subcellular distribution of BDNF, TrkB and CaMKII‐β mRNAs; reduction of CaMKII‐α mRNA dendritic staining, as compared with unstimulated kindled animals. Conclusions: Data provide evidence that BDNF, TrkB, and CaMKII‐α and ‐β 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.