Genetic background regulates semaphorin gene expression and epileptogenesis in mouse brain after kainic acid status epilepticus.
The host response to neural injury, which can include axonal sprouting and synaptic reorganization is likely to be under tight genetic regulatory control at the level of the genome and may be implicated in epileptogenesis. Despite its importance, however, the molecular basis of synaptic reorganization is unclear. We have studied the development of synaptic reorganization, semaphorin gene expression, and epileptogenesis in hippocampus of epileptogenic sensitive (FVB/NJ) and epileptogenic resistant (C57BL/6J) mice (i.e. distinct genetic backgrounds) after kainic acid-induced status epilepticus. Our results support the hypothesis that disruption of transcriptional regulation of axon guidance genes leads to a differential loss of tonic neuropilin-2 dependent activation of semaphorin 3F receptors on hippocampal neurons on distinct genetic backgrounds. This results in rearranged synaptic circuitry and thus promotes epileptogenesis. These findings may define biologic principles underlying the role of semaphorin signaling which may broadly apply to other systems undergoing neural regeneration.
Yang
J
J
Department of Neurology, University of Kentucky College of Medicine, Lexington, KY, USA.
Houk
B
B
Shah
J
J
Hauser
K F
KF
Luo
Y
Y
Smith
G
G
Schauwecker
E
E
Barnes
G N
GN
D000818:Animals; D001369:Axons / Q000378:metabolism; D015152:Blotting, Northern; D001923:Brain Chemistry / Q000235:genetics*; D002452:Cell Count; D003001:Cloning, Molecular; D018891:Dentate Gyrus / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists; D019922:GAP-43 Protein / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007608:Kainic Acid; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011712:Pyramidal Tracts / Q000378:metabolism; D015347:RNA Probes; D039961:Semaphorins / Q000096:biosynthesis* / Q000235:genetics; D013045:Species Specificity; D013226:Status Epilepticus / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000502:physiology
D018690:Excitatory Amino Acid Agonists; D019922:GAP-43 Protein; D015347:RNA Probes; D039961:Semaphorins; D003847:Deoxyglucose; D007608:Kainic Acid