RNA Sequencing Reveals Region-specific Molecular Mechanisms Associated with Epileptogenesis in a Model of Classical Hippocampal Sclerosis

Overview

Journal Sci Rep

Specialty Science

Date 2016 Mar 4

PMID 26935982

Citations 8

Authors

A S Vieira

A H de Matos

A M do Canto

C S Rocha

B S Carvalho

V D B Pascoal

B Norwood

S Bauer

F Rosenow

R Gilioli

F Cendes

I Lopes-Cendes

Affiliations

Soon will be listed here.

Abstract

We report here the first complete transcriptome analysis of the dorsal (dDG) and ventral dentate gyrus (vDG) of a rat epilepsy model presenting a hippocampal lesion with a strict resemblance to classical hippocampal sclerosis (HS). We collected the dDG and vDG by laser microdissection 15 days after electrical stimulation and performed high-throughput RNA-sequencing. There were many differentially regulated genes, some of which were specific to either of the two sub-regions in stimulated animals. Gene ontology analysis indicated an enrichment of inflammation-related processes in both sub-regions and of axonal guidance and calcium signaling processes exclusively in the vDG. There was also a differential regulation of genes encoding molecules involved in synaptic function, neural electrical activity and neuropeptides in stimulated rats. The data presented here suggests, in the time point analyzed, a remarkable interaction among several molecular components which takes place in the damaged hippocampi. Furthermore, even though similar mechanisms may function in different regions of the DG, the molecular components involved seem to be region specific.

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References

Baraban S, Tallent M . Interneuron Diversity series: Interneuronal neuropeptides--endogenous regulators of neuronal excitability. Trends Neurosci. 2004; 27(3):135-42. DOI: 10.1016/j.tins.2004.01.008. View

Hart S, Therneau T, Zhang Y, Poland G, Kocher J . Calculating sample size estimates for RNA sequencing data. J Comput Biol. 2013; 20(12):970-8. PMC: 3842884. DOI: 10.1089/cmb.2012.0283. View

Baraban S . Neuropeptide Y and epilepsy: recent progress, prospects and controversies. Neuropeptides. 2004; 38(4):261-5. DOI: 10.1016/j.npep.2004.04.006. View

Peng Z, Huang C, Stell B, Mody I, Houser C . Altered expression of the delta subunit of the GABAA receptor in a mouse model of temporal lobe epilepsy. J Neurosci. 2004; 24(39):8629-39. PMC: 6729896. DOI: 10.1523/JNEUROSCI.2877-04.2004. View

Andersen P, Holmqvist B, VOORHOEVE P . Entorhinal activation of dentate granule cells. Acta Physiol Scand. 1966; 66(4):448-60. DOI: 10.1111/j.1748-1716.1966.tb03223.x. View

Turski W, Cavalheiro E, Schwarz M, Czuczwar S, Kleinrok Z, Turski L . Limbic seizures produced by pilocarpine in rats: behavioural, electroencephalographic and neuropathological study. Behav Brain Res. 1983; 9(3):315-35. DOI: 10.1016/0166-4328(83)90136-5. View

Tauck D, Nadler J . Evidence of functional mossy fiber sprouting in hippocampal formation of kainic acid-treated rats. J Neurosci. 1985; 5(4):1016-22. PMC: 6565006. View

Sloviter R . Decreased hippocampal inhibition and a selective loss of interneurons in experimental epilepsy. Science. 1987; 235(4784):73-6. DOI: 10.1126/science.2879352. View

Wang J, Rojas C, Zhou J, SCHWARTZ L, Nicholas H, Hoffman E . Sequence and genomic structure of the human adult skeletal muscle sodium channel alpha subunit gene on 17q. Biochem Biophys Res Commun. 1992; 182(2):794-801. DOI: 10.1016/0006-291x(92)91802-w. View

10.

Stanley B, Magdalin W, Seirafi A, Nguyen M, Leibowitz S . Evidence for neuropeptide Y mediation of eating produced by food deprivation and for a variant of the Y1 receptor mediating this peptide's effect. Peptides. 1992; 13(3):581-7. DOI: 10.1016/0196-9781(92)90093-i. View

11.

Poirier J, Baccichet A, Dea D, Gauthier S . Cholesterol synthesis and lipoprotein reuptake during synaptic remodelling in hippocampus in adult rats. Neuroscience. 1993; 55(1):81-90. DOI: 10.1016/0306-4522(93)90456-p. View

12.

Musso T, Johnston J, Linnekin D, Varesio L, Rowe T, Oshea J . Regulation of JAK3 expression in human monocytes: phosphorylation in response to interleukins 2, 4, and 7. J Exp Med. 1995; 181(4):1425-31. PMC: 2191962. DOI: 10.1084/jem.181.4.1425. View

13.

Kato H, Kogure K, Liu X, Araki T, Itoyama Y . Progressive expression of immunomolecules on activated microglia and invading leukocytes following focal cerebral ischemia in the rat. Brain Res. 1996; 734(1-2):203-12. View

14.

Eglitis M, Mezey E . Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci U S A. 1997; 94(8):4080-5. PMC: 20571. DOI: 10.1073/pnas.94.8.4080. View

15.

Parent J, Yu T, Leibowitz R, Geschwind D, Sloviter R, Lowenstein D . Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci. 1997; 17(10):3727-38. PMC: 6573703. View

16.

Fanselow M, Dong H . Are the dorsal and ventral hippocampus functionally distinct structures?. Neuron. 2010; 65(1):7-19. PMC: 2822727. DOI: 10.1016/j.neuron.2009.11.031. View

17.

Norwood B, Bumanglag A, Osculati F, Sbarbati A, Marzola P, Nicolato E . Classic hippocampal sclerosis and hippocampal-onset epilepsy produced by a single "cryptic" episode of focal hippocampal excitation in awake rats. J Comp Neurol. 2010; 518(16):3381-407. PMC: 2894278. DOI: 10.1002/cne.22406. View

18.

Sangameswaran L, Fish L, Koch B, Rabert D, Delgado S, Ilnicka M . A novel tetrodotoxin-sensitive, voltage-gated sodium channel expressed in rat and human dorsal root ganglia. J Biol Chem. 1997; 272(23):14805-9. DOI: 10.1074/jbc.272.23.14805. View

19.

Lurton D, Cavalheiro E . Neuropeptide-Y immunoreactivity in the pilocarpine model of temporal lobe epilepsy. Exp Brain Res. 1997; 116(1):186-90. DOI: 10.1007/pl00005739. View

20.

Skaliora I, Singer W, Betz H, Puschel A . Differential patterns of semaphorin expression in the developing rat brain. Eur J Neurosci. 1998; 10(4):1215-29. DOI: 10.1046/j.1460-9568.1998.00128.x. View