Concurrent immediate early gene induction by epileptic seizures in heterotopic cortical grafts and neocortex.
Cortical primordia of rat fetuses (gestation day 14) were stereotactically grafted into the rostral striatum of adult recipient rats. After 8 weeks, the transplants had developed into a highly differentiated population of mature neuroectodermal cells. Host rats were then subjected to 15 min of bicuculline-induced epileptic seizures or served as controls. Seizure-elicited immediate early gene (IEG) expression was investigated after various postictal survival times (up to 24 h), using immunocytochemistry with specific antisera against seven IEG encoded proteins (c-FOS, FOS B, c-JUN, JUN B, JUN D, KROX-24, KROX-20). Constitutive IEG expression in intra striatum grafted neocortical neurons was identical to that in the corresponding host neocortex. In particular, abundant KROX-24 and lack of c-JUN expression implies the establishment of synaptic contacts within the graft or with the host circuitry. Postictal expression kinetics of individual IEG encoded proteins within the transplants were strikingly similar to those seen in the neocortex in situ. c-FOS and KROX-24 were most rapidly induced, followed by c-JUN and JUN B, and a more delayed induction of FOS B, JUN D and KROX-20. Apart from a slightly prolonged c-FOS expression in grafts, individual transcription factors remained elevated for different time periods and showed a concurrent decline in transplants and in neocortex in situ. In conclusion, IEG induction in grafts closely paralleled that in the host neocortex but differed from the adjacent striatum which exhibited no c-JUN induction at any time point investigated. These results indicate that following an appropriate differentiation period, heterotopically grafted embryonic cortical neurons respond to extracellular stimuli with changes of gene expression that closely resemble the normal host cortex. This suggests development of a similar molecular phenotype, including proper acquisition and intracellular processing of information.
Department of Neuropathology, University of Heidelberg, FRG.
S
S
Bele
P
P
Gass
T
T
Herdegen
R
R
Bravo
M
M
Kiessling
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism / Q000637:transplantation*; D004827:Epilepsy / Q000378:metabolism*; D005260:Female; D005815:Genetic Code; D011518:Proto-Oncogene Proteins / Q000032:analysis; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis; D051381:Rats; D013997:Time Factors; D014158:Transcription, Genetic; D016042:Transplantation, Heterotopic / Q000502:physiology*
D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun