Effect of cytokine treatment on the neurogenesis process in the brain of soman-poisoned mice.
We previously described that enhanced proliferation of neural progenitors occurred in the subgranular zone (SGZ) of the dentate gyrus and in the subventricular zone (SVZ) of the mouse brain following soman poisoning. Then, a discrete number of these cells seemed to migrate and engraft into the main damaged brain regions (hippocampus; septum and amygdala) and subsequently differentiate into neurons. In the present study, the effect of a cytokine treatment on the neurogenesis process was evaluated. For this purpose, subcutaneous injection of a cocktail of 40 microg/kg epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) was administered daily to soman-poisoned mice (110 microg/kg soman and 5.0 mg/kg methyl nitrate atropine), from post-soman days 1 to 8. To label replicating neural progenitors, 200 mg/kg bromodeoxyuridine (BrdU) was injected twice a day between post-soman days 6 and 8. Mice were sacrificed on post-soman day 9 or 34. On post-soman day 9, the cytokine treatment had no effect on the proliferation of neural progenitors in the SVZ and SGZ, as assessed by BrdU immunochemistry. However, this treatment seemed to promote the migration of neural precursor cells from the proliferative areas towards damaged brain regions. Indeed, in the CA1 hippocampal layer of soman-poisoned mice, on post-soman day 34, the cytokine treatment increased the number of healthy pyramidal neurons stained by hemalun-eosin dye. The cytokine treatment also augmented the number of BrdU-labeled cells in the CA1 hippocampal layer and amygdala. Interestingly, the administration of cytokines resulted in the differentiation of BrdU-positive cells into new neurons in the CA1 hippocampal layer, whereas astrocytic differentiation was preferentially observed in the amygdala.
Collombet
Jean-Marc
JM
Département de Toxicologie, CRSSA-B.P. 87-38702 LA Tronche, France. jmcollombet@crssa.net
Four
Elise
E
Burckhart
Marie-France
MF
Masqueliez
Catherine
C
Bernabé
Denis
D
Baubichon
Dominique
D
Hérodin
Francis
F
Lallement
Guy
G
D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D002552:Cerebral Ventricles / Q000187:drug effects / Q000473:pathology; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004396:Coloring Agents; D004268:DNA-Binding Proteins; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000032:analysis; D012999:Soman / Q000633:toxicity*; D013234:Stem Cells / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors
D002800:Cholinesterase Inhibitors; D004396:Coloring Agents; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D018696:Neuroprotective Agents; D009687:Nuclear Proteins; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D012999:Soman; D001973:Bromodeoxyuridine