Protection against inflammatory neurodegeneration and glial cell death by 7beta-hydroxy epiandrosterone, a novel neurosteroid.
It has been demonstrated that neuroprotective effects of dehydroepiandrosterone (DHEA) may be mediated by its 7alpha- and 7beta-hydroxy derivatives. Epiandrosterone is also converted to 7beta-hydroxy epiandrosterone (7beta-OH EPIA) in numerous tissues. The aim of the present study was to establish whether treatment with 7beta-hydroxy epiandrosterone has a neuroprotective effect in animal models of Alzheimer's disease (AD) lesions. Intra-amygdaloid administration of amyloid beta [Abeta(25-35)] increased the number of tau-positive cells in the ipsilateral hippocampus. Intracerebroventricular administration of ethylcholine aziridinium (AF64A) caused cholinergic damage in the septum, and glial lesions in the lateral septal nucleus and in the lateral zones of the hippocampus. These effects were almost completely prevented when animals were treated subcutaneously (b.i.d.) for 10 days with 0.1 mg/kg 7beta-hydroxy epiandrosterone. These findings indicate that 7beta-hydroxy epiandrosterone has powerful cytoprotective effects suggesting that (a) this neurosteroid may have therapeutic potential in various neurodegenerative conditions such as Alzheimer's disease, and (b) 7beta-hydroxy steroids may constitute a novel class of endogenous neuroprotective agents.
Dudas
Bertalan
B
Lake Erie College of Osteopathic Medicine, Maywood, IL 16509, USA. bdudas@lecom.edu
Hanin
Israel
I
Rose
M
M
Wülfert
Ernst
E
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity; D000818:Animals; D001388:Aziridines / Q000037:antagonists & inhibitors / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology; D002794:Choline / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000633:toxicity; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000187:drug effects / Q000473:pathology; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D012686:Septal Nuclei / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016875:tau Proteins / Q000187:drug effects / Q000378:metabolism
D016229:Amyloid beta-Peptides; D001388:Aziridines; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D016875:tau Proteins; D003687:Dehydroepiandrosterone; C003587:7-hydroxydehydroepiandrosterone; C044894:ethylcholine aziridinium; D002795:Choline O-Acetyltransferase; D002794:Choline