Nasal administration of cholera toxin B subunit-nerve growth factor improves the space learning and memory abilities in beta-amyloid protein(25-35)-induced amnesic mice.
Nerve growth factor (NGF) is a potential drug for Alzheimer's disease treatment, but delivering NGF to the brain is difficult. To increase the content of NGF in brain, we prepared cholera toxin B subunit (CB) -NGF by the improved sodium metaperiodate method and compared its pharmacodynamics with NGF. In vitro, CB-NGF, as well as NGF, could promote neurite outgrowth and increase choline acetyltransferase activities. But the time window of TrkA phosphorylation induced by CB-NGF and NGF was different. In vivo, nasal administration of CB-NGF could increase the stay time and partially improve abilities of space learning and memory in amnesic mice, and protected the cholinergic neurons in basal forebrain against Abeta(25-35). CB-NGF treatment has better curative effects than NGF in Alzheimer's disease model mice.
Zhang
Q
Q
Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.
Liu
Y
Y
Yang
N
N
Wan
X
X
Zuo
P
P
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002772:Cholera Toxin / Q000008:administration & dosage*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D007858:Learning / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D020932:Nerve Growth Factor / Q000008:administration & dosage*; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects; D010446:Peptide Fragments; D051381:Rats; D013028:Space Perception / Q000187:drug effects*; D013997:Time Factors
D000276:Adjuvants, Immunologic; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D002772:Cholera Toxin; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase