ABSTRACT
The time course of induction of the proto-oncogene c-fos and the inducible heat shock hsp70 gene was studied from 5 minutes to 24 hours at both transcriptional (c-fos and hsp70 mRNA) and translational levels (C-FOS and HSP72 proteins) in the rat hippocampus and piriform cortex (Pir) after soman-induced seizures. Induction of c-fos was noticed as early as 5 minutes after seizures onset in all fields of hippocampal formation (CA1, CA3, CA4, and dentate gyrus) and in piriform cortex. The most intense induction was observed in piriform cortex. A sustained activation of c-fos occurred in Pir and in CA1, CA3, and CA4 areas of hippocampus. Nevertheless, histological analysis showed rare affected neurons in CA4, whereas damage was severe in Pir and in CA1 and CA3 hippocampal subfields. Induction of hsp70 mRNA occurred but was delayed in all areas previously exhibiting c-fos expression. Nevertheless HSP72 protein was never expressed in the structures where injury was high (i.e., CA1 and piriform cortex) and mainly occurred in the less damaged structure (i.e., CA4 area of hippocampus). Regional expression of glial fibrillary acidic protein mRNA was also studied in order to exclude an astroglial origin of the c-fos and hsp70 gene inductions. Our results demonstrated that after soman induced-seizures 1) there was no strict correlation between time course or intensity of neuronal c-fos induction and subsequent neuropathology, and 2) the most lesioned areas did not express HSP72 protein in spite of intense mRNA induction, suggesting that transcriptional and translational events for hsp70 gene might vary according to the severity of seizure insult.
Subject(s)
Cerebral Cortex/metabolism , HSP70 Heat-Shock Proteins/biosynthesis , Hippocampus/metabolism , Proto-Oncogene Proteins c-fos/biosynthesis , Seizures/metabolism , Animals , Astrocytes/metabolism , Cerebral Cortex/cytology , Convulsants , Hippocampus/cytology , Image Processing, Computer-Assisted , Immunohistochemistry , In Situ Hybridization , Male , Neurons/metabolism , Rats , Rats, Wistar , Seizures/chemically induced , SomanABSTRACT
The central toxicities of two potassium ion channel blockers, apamin and alpha-dendrotoxin (DTx), have been compared. Both apamin and dendrotoxin injected intracerebroventricularly produced signs of poisoning, including tremor and ataxia; however, only DTx produced changes in brain electrical activity, with high voltage spikes and epileptiform activity and subsequent brain damage. DTx, but not apamin, increased the amplitude of evoked field potentials and caused repetitive firing of neurones in hippocampal slices. Signs of poisoning following peripheral (intraperitoneal) administration of apamin were similar to those following central administration, including dramatic haemorrhagic effects on the lungs of decedent animals. These results are consistent with dendrotoxin being a centrally-active neurotoxin producing epileptiform activity and brain damage, whilst apamin produces its most significant pathology in the lung, possibly involving a neurogenic mechanism.
Subject(s)
Apamin/toxicity , Brain/drug effects , Elapid Venoms/toxicity , Neurotoxins/toxicity , Potassium Channel Blockers , Animals , Apamin/administration & dosage , Ataxia/chemically induced , Brain/pathology , Brain/physiopathology , Disease Models, Animal , Elapid Venoms/administration & dosage , Electric Stimulation , Electroencephalography , Electrophysiology , Hemorrhage/chemically induced , Hippocampus/drug effects , Hippocampus/pathology , Hippocampus/physiopathology , In Vitro Techniques , Injections, Intraperitoneal , Injections, Intraventricular , Lung/drug effects , Lung/pathology , Male , Neurons/drug effects , Neurotoxins/administration & dosage , Rats , Rats, Wistar , Tremor/chemically inducedABSTRACT
We investigated the time course of GFAP levels in the hippocampal formation during the first 24 h following soman intoxication in rats. GFAP mRNA expression was detected by in situ hybridization. Intense GFAP mRNA expression was present in the molecular layer of the dentate gyrus as early as 6 h after intoxication. This expression was comparatively lower in other dentate gyrus layers and hippocampal CA1, CA3 and CA4 areas and seemed to be related to excessive neuronal activity. Histopathological examination demonstrated that GFAP expression in dentate gyrus is not correlated with lesions. The high astrocytic reactivity in the molecular layer of the dentate gyrus is discussed in relation to the maintenance of the homeostasis of glutamate and of synaptic plasticity in this area during soman intoxication.
