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Expression of brain‐derived neurotrophic factor and structural plasticity in the dentate gyrus and CA 2 region correlate with epileptiform activity
Author(s) -
Tulke Susanne,
Haas Carola A.,
Häussler Ute
Publication year - 2019
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.15540
Subject(s) - dentate gyrus , neuroscience , neuroplasticity , brain derived neurotrophic factor , neurotrophic factors , synaptic plasticity , plasticity , hippocampus , psychology , medicine , receptor , physics , thermodynamics
Objective Hippocampal sclerosis is a hallmark of mesial temporal lobe epilepsy ( MTLE ), comprising gliosis and neuronal loss in the hippocampus. However, dentate granule cells and CA 2 pyramidal cells ( PC s) survive, as they share physiological characteristics that may render them less sensitive to hyperexcitation in MTLE . Here, we asked whether both engage similar molecular plasticity mechanisms to support their resilience in MTLE . We chose brain‐derived neurotrophic factor ( BDNF ), correlated the expression with activity, and used neuropeptide Y ( NPY ) and principal cell dispersion as plasticity readout. Methods Adult male mice received a unilateral intrahippocampal kainate injection to induce status epilepticus ( SE ) and bilateral electrodes into the dentate gyrus and CA 2 for in vivo recordings and quantification of epileptiform activity. To assess the time course of Bdnf mRNA expression in these regions, we performed fluorescence in situ hybridization, complemented by immunohistochemistry for NPY and quantification of principal cell dispersion. Results We show that Bdnf expression was transiently up‐regulated during SE in the granule cell layer ( GCL ) and CA 2 and, after a slight reduction at 2 days, increased persistently in both regions ipsilaterally. Intrahippocampal recordings revealed a threshold for the duration of SE to induce these changes. Recurrent epileptiform activity developed in the ipsilateral dentate gyrus and CA 2 over time and was correlated with Bdnf mRNA levels, although more pronounced in the dentate gyrus. The dispersion of the GCL and CA 2 correlated with Bdnf mRNA expression. NPY protein expression was only increased in granule cells and mossy fibers, remaining unchanged in CA 2. Significance Our study reveals differential molecular plasticity changes in granule cells and CA 2 PC s despite many similarities (epileptiform activity, somatic mossy fiber input, dispersion). These findings contribute to the understanding of common as well as individual characteristics of the cell populations underlying the epileptic hippocampal network.