Unexpected expression of orexin-B in basal conditions and increased levels in the adult rat hippocampus during pilocarpine-induced epileptogenesis.
Orexin-A (OX-A) and -B (OX-B) peptides present in the hippocampus are considered to be exclusively contained in fibers arising from hypothalamus neurons, which were established as the only source of orexins (OXs). Because OX-A is known to exert excitatory actions in the hippocampus, we hypothesized that the level of OXs targeted toward the hippocampus may be increased following status-epilepticus (SE)-induced epileptogenesis in the rat pilocarpine model of temporal lobe epilepsy. We found that tissue concentration of prepro-OX mRNA, which encodes for both peptides, rapidly decreased in the hypothalamus of rats having experienced pilocarpine-induced SE (Pilo-SE) followed by a reduced density of OX-A and OX-B immunopositive fibers arising from these neurons. By contrast, it was unexpected to detect within the hippocampus the presence of prepro-OX mRNA in basal conditions and to evidence its up-regulation during the 1- to 3-day period following Pilo-SE. The number of prepro-OX mRNA copies determined by real-time RT-PCR was approximately 50-fold lower in the hippocampus than that in the hypothalamus, precluding the use of in situ hybridization to localize the cells which synthesize the transcript within the hippocampus. The increase in prepro-OX mRNA level within the hippocampus was accompanied by the detection of OX-B-like immunoreactivity 2-3 days post-SE, not only in pyramidal neurons, granule cells and cell bodies resembling interneurons, but also in some astrocytes scattered throughout the hippocampus. The present data suggest that the gene encoding OXs can be activated in the hippocampus, which may play a role in the pathogenesis of epilepsy.
Morales
Anne
A
Laboratoire de Physiologie Intégrative Cellulaire et Moléculaire, UMR 5123 CNRS and Université Claude Bernard Lyon 1, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne Cedex, France. morales@univ-lyon1.fr
Bonnet
Chantal
C
Bourgoin
Naïck
N
Touvier
Thierry
T
Nadam
Jérémie
J
Laglaine
Aël
A
Navarro
Fabrice
F
Moulin
Colette
C
Georges
Béatrice
B
Pequignot
Jean-Marc
JM
Bezin
Laurent
L
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D004327:Drinking Behavior / Q000187:drug effects; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D005247:Feeding Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D018721:Muscarinic Agonists; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D000068797:Orexins; D010862:Pilocarpine; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D047908:Intracellular Signaling Peptides and Proteins; D018721:Muscarinic Agonists; D009479:Neuropeptides; D000068797:Orexins; D012333:RNA, Messenger; D010862:Pilocarpine