Neuroprotective effects of melatonin upon the offspring cerebellar cortex in the rat model of BCNU-induced cortical dysplasia.
Cortical dysplasia is a malformation characterized by defects in proliferation, migration and maturation. This study was designed to evaluate the alterations in offspring rat cerebellum induced by maternal exposure to carmustine-[1,3-bis (2-chloroethyl)-1-nitrosoure] (BCNU) and to investigate the effects of exogenous melatonin upon cerebellar BCNU-induced cortical dysplasia, using histological and biochemical analyses. Pregnant Wistar rats were assigned to five groups: intact-control, saline-control, melatonin-treated, BCNU-exposed and BCNU-exposed plus melatonin. Rats were exposed to BCNU on embryonic day 15 and melatonin was given until delivery. Immuno/histochemistry and electron microscopy were carried out on the offspring cerebellum, and levels of malondialdehyde and superoxide dismutase were determined. Histopathologically, typical findings were observed in the cerebella from the control groups, but the findings consistent with early embryonic development were noted in BCNU-exposed cortical dysplasia group. There was a marked increase in the number of TUNEL positive cells and nestin positive cells in BCNU-exposed group, but a decreased immunoreactivity to glial fibrillary acidic protein, synaptophysin and transforming growth factor beta1 was observed, indicating a delayed maturation, and melatonin significantly reversed these changes. Malondialdehyde level in BCNU-exposed group was higher than those in control groups and melatonin decreased malondialdehyde levels in BCNU group (P<0.01), while there were no significant differences in the superoxide dismutase levels between these groups. These data suggest that exposure of animals to BCNU during pregnancy leads to delayed maturation of offspring cerebellum and melatonin protects the cerebellum against the effects of BCNU.
Uyanikgil
Yiğit
Y
Department of Histology and Embryology, Ege University School of Medicine, TR-35100 Izmir, Turkey.
Baka
Meral
M
Ateş
Utku
U
Turgut
Mehmet
M
Yavaşoğlu
Altuğ
A
Ulker
Sibel
S
Sözmen
Eser Yildirim
EY
Sezer
Ebru
E
Elmas
Ciğdem
C
Yurtseven
Mine Ertem
ME
D000818:Animals; D000831:Animals, Newborn; D001927:Brain Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002330:Carmustine; D002525:Cerebellar Cortex / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D005260:Female; D020287:In Situ Nick-End Labeling / Q000379:methods; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000627:therapeutic use*; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D053773:Transforming Growth Factor beta1; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D001973:Bromodeoxyuridine; D008550:Melatonin; D002330:Carmustine