Oral administration of idebenone induces nerve growth factor in the brain and improves learning and memory in basal forebrain-lesioned rats.
Nerve growth factor plays an important role in the survival and maintenance of cholinergic neurons in the central neuronal system. In senile dementia of the Alzheimer type, learning and memory are impaired by the loss of neurons in the magnocellular cholinergic neuronal system. It is therefore, of interest to investigate the role of nerve growth factor in this degenerative disorder. Since nerve growth factor does not cross the blood-brain barrier and is easily metabolized by peptidases when administered peripherally, it can be used for medical treatment only when directly injected into the brain. We demonstrate here that the oral administration of idebenone, a potent in vitro nerve growth factors synthesis stimulator, induced an increase in nerve growth factor protein and mRNA, and in choline acetyltransferase activity, in basal forebrain lesioned rats, but not in intact rats. Idebenone also ameliorated the behavioral deficits in habituation, water maze, and passive avoidance tasks in these animals. These results suggest that idebenone stimulated nerve growth factor synthesis in vivo and ameliorates the behavioral deficits which were accompanied with the recovery of the reduced choline acetyltransferase activity in the basal forebrain-lesioned rats.
Nitta
A
A
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Japan.
Murakami
Y
Y
Furukawa
Y
Y
Kawatsura
W
W
Hayashi
K
K
Yamada
K
K
Hasegawa
T
T
Nabeshima
T
T
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001483:Base Sequence; D016227:Benzoquinones / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D007858:Learning / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects*; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000187:drug effects; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D016548:Prosencephalon / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013028:Space Perception / Q000187:drug effects; D014451:Ubiquinone / Q000031:analogs & derivatives
D016227:Benzoquinones; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D014451:Ubiquinone; D002795:Choline O-Acetyltransferase; C036619:idebenone