Adrenalectomy-induced cell death in the dentate gyrus: further characterisation using TUNEL and effects of the Ginkgo biloba extract, EGb 761, and ginkgolide B.
This study investigated the potential neuroprotective effects of the Ginkgo biloba extract, EGb-761, and ginkgolide B, on adrenalectomy (ADX)-induced cell death in the dentate gyrus (DG). Adrenalectomised, sham surgery-treated, and naive controls received either EGb-761 (25, 50, or 100 mg/kg), 0.9% saline vehicle control, ginkgolide B (10 or 25 mg/kg), or a polyethylene glycol vehicle control, i.p, daily for 6 days postsurgery. Cell death in the DG was determined by in situ labelling of DNA fragments, using the TUNEL method; sections were counterstained with hematoxylin. Radioimmunoassay was used to confirm a decrease in plasma corticosterone (CORT) after ADX. TUNEL-positive granule cells were observed in the DG at 1 week, but not at 24 h, post-ADX. The rate of granule cell death at this time was highest in the suprapyramidal blade and increased in a crest tip and a rostrotemporal gradient. Whereas CORT replacement completely prevented the occurrence of TUNEL-positive granule cells, EGb-761 and ginkgolide B did not, at any of the doses used. These results suggest that these drugs may not have substantial neuroprotective effects in the ADX model of neurodegeneration.
Maclennan
Karyn M
KM
Department of Pharmacology and Toxicology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Zheng
Yiwen
Y
Sheard
Philip W
PW
Williams
Sheila M
SM
Darlington
Cynthia L
CL
Smith
Paul F
PF
D000315:Adrenalectomy; D000818:Animals; D002452:Cell Count; D016923:Cell Death / Q000502:physiology; D003345:Corticosterone / Q000378:metabolism / Q000494:pharmacology; D018891:Dentate Gyrus / Q000473:pathology*; D004224:Diterpenes; D020441:Ginkgo biloba; D046934:Ginkgolides; D020249:Hormone Replacement Therapy; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D007783:Lactones / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain / Q000187:drug effects; D000096983:Ginkgo Extract
D003345:Corticosterone; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D018696:Neuroprotective Agents; D010936:Plant Extracts; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C045856:ginkgolide B