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

Q Zhang; Y Liu; N Yang; X Wan; P Zuo

doi:10.1016/j.neuroscience.2008.05.040

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

Neuroscience. 2008 Jul 31;155(1):234-40. doi: 10.1016/j.neuroscience.2008.05.040. Epub 2008 Jun 5.

Authors

Q Zhang¹, Y Liu, N Yang, X Wan, P Zuo

Affiliation

¹ Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.

PMID: 18585441
DOI: 10.1016/j.neuroscience.2008.05.040

Abstract

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.

MeSH terms

Adjuvants, Immunologic / administration & dosage*
Administration, Intranasal
Amnesia / chemically induced
Amnesia / drug therapy*
Amyloid beta-Peptides / chemistry
Amyloid beta-Peptides / toxicity
Animals
Behavior, Animal / drug effects
Cholera Toxin / administration & dosage*
Choline O-Acetyltransferase / metabolism
Disease Models, Animal
Dose-Response Relationship, Drug
Gene Expression Regulation / drug effects
Learning / drug effects*
Male
Maze Learning / drug effects
Mice
Mice, Inbred BALB C
Nerve Growth Factor / administration & dosage*
Neurites / drug effects
Neurites / physiology
PC12 Cells / cytology
PC12 Cells / drug effects
Peptide Fragments
Rats
Space Perception / drug effects*
Time Factors

Substances

Adjuvants, Immunologic
Amyloid beta-Peptides
Peptide Fragments
Cholera Toxin
Nerve Growth Factor
Choline O-Acetyltransferase