Abstract
Ten days treatment with nicotine reduced insoluble amyloid A beta 1-40 and Alpha beta 1-42 peptides by 80% in the cortex of 9-month-old APPsw mice, which is more than that observed in 14.5-month-old mice following nicotine treatment for 5.5 months. A reduction in A beta associated with cerebral vessels was observed in addition to that deposited as parenchymal plaques after 5.5 months treatment. The diminution in A beta peptides observed was not accompanied by changes in brain alpha, beta or gamma secretase-like activities, NGF or BDNF protein expression measured in brain homogenates. A significant increase in sAPP was observed after nicotine treatment of SH-SY5Yneuroblastoma cells that could be blocked by the nicotinic antagonist mecamylamine. Attenuation of elevated [(125)I]-alpha bungarotoxin binding (alpha 7) in APPsw mice was observed after 5.5 months nicotine treatment. Both these observations suggest that the reduction in insoluble A beta by nicotine might be in part mediated via the alpha 7 nicotinic receptor. Further studies are required to identify potential mechanisms of the nicotine's amyloid-reducing effect.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Age Factors
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Amyloid Precursor Protein Secretases
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Amyloid beta-Peptides / analysis
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Amyloid beta-Peptides / blood
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Amyloid beta-Peptides / metabolism*
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Amyloid beta-Protein Precursor / genetics
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Amyloid beta-Protein Precursor / metabolism
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Animals
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Aspartic Acid Endopeptidases
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Blood Vessels / drug effects*
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Blotting, Western / methods
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Brain / drug effects*
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Brain / metabolism
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Brain Chemistry
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Brain-Derived Neurotrophic Factor / metabolism
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Bungarotoxins / pharmacokinetics
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Cell Line, Tumor
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Cerebral Arteries / drug effects*
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Cerebral Arteries / metabolism
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Drug Administration Schedule
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Embryo, Mammalian
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Endopeptidases / metabolism
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Glucose Transporter Type 1
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Humans
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Immunohistochemistry / methods
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Iodine Isotopes / pharmacokinetics
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Monosaccharide Transport Proteins / metabolism
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Nerve Growth Factor / metabolism
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Neuroblastoma
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Nicotine / administration & dosage*
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Nicotine / pharmacology
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Peptide Fragments / analysis
Substances
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Amyloid beta-Peptides
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Amyloid beta-Protein Precursor
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Brain-Derived Neurotrophic Factor
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Bungarotoxins
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Glucose Transporter Type 1
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Iodine Isotopes
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Monosaccharide Transport Proteins
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Peptide Fragments
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SLC2A1 protein, human
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amyloid beta-protein (1-40)
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amyloid beta-protein (1-42)
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Nicotine
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Nerve Growth Factor
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Amyloid Precursor Protein Secretases
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Endopeptidases
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Aspartic Acid Endopeptidases
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BACE1 protein, human
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Bace1 protein, mouse