Activation of brain metabolism and fos during limbic seizures: the role of locus coeruleus.
The noradrenergic nucleus Locus Coeruleus (LC) densely innervates limbic structures. In rats, the damage to LC by the neurotoxin DSP-4, converts episodic limbic seizures induced by bicuculline infusion in the anterior piriform cortex (APC) into self-sustaining status epilepticus (SE). SE induced by this approach is similar to SE induced by co-infusing cyclothiazide and bicuculline into APC in rats bearing an intact LC. As opposed to other commonly used rat SE models (e.g. systemic kainate or pilocarpine), this approach allows one to analyze the effects of SE on brain regions which are solely due to spreading of seizure activity, rather than to direct effect of systemic chemoconvulsant. We evaluated the expression of Fos protein (an immediate early gene product), and the local cerebral metabolic rates for [14C] 2-deoxyglucose (lCMRglc), in rats following SE induced either by cyclothiazide+bicuculline or by DSP-4+bicuculline. We demonstrated that regional Fos expression after SE does not parallel the increase in lCMRglc, in LC-lesioned rats. In DSP-4+bicuculline rats there is an overall lower expression of the protein as compared with the cyclothiazide+bicuculline or bicuculline alone groups; even more, such a difference co-exists with an higher lCMRglc in the DSP-4+bicuculline-treated rats in some regions, as compared with the other groups. These data show that LC neurons play an important role in determining immediate early genes expression even in conditions of strong pathological activation, such as limbic SE. This might have relevant effects in the plastic mechanisms related with epileptogenesis.
Giorgi
Filippo S
FS
Department of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy; Department of Neurosciences, Section of Neurology, University of Pisa, Pisa, Italy; Centro Studi e Ricerche 'E. Fermi', Roma, Italy.
Blandini
Fabio
F
Laboratory of Functional Neurochemistry, Neurological Institute 'C. Mondino', Pavia, Italy.
Cantafora
Emanuela
E
Department of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy.
Biagioni
Francesca
F
Laboratory of Neurobiology of Movement Disorders I.R.C.C.S., INM, Neuromed, Pozzilli, Isernia, Italy.
Armentero
Marie-Therese
MT
Laboratory of Functional Neurochemistry, Neurological Institute 'C. Mondino', Pavia, Italy.
Pasquali
Livia
L
Department of Neurosciences, Section of Neurology, University of Pisa, Pisa, Italy.
Orzi
Francesco
F
Department of Neurological Sciences, University of Rome 'La Sapienza', Roma, Italy.
Murri
Luigi
L
Department of Neurosciences, Section of Neurology, University of Pisa, Pisa, Italy.
Paparelli
Antonio
A
Department of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy.
Fornai
Francesco
F
Department of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy; Laboratory of Neurobiology of Movement Disorders I.R.C.C.S., INM, Neuromed, Pozzilli, Isernia, Italy. Electronic address: f.fornai@med.unipi.it.
D000818:Animals; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry / Q000235:genetics; D017781:Genes, Immediate-Early / Q000502:physiology; D008032:Limbic System / Q000378:metabolism*; D008125:Locus Coeruleus / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures
D016760:Proto-Oncogene Proteins c-fos; D009638:Norepinephrine