Nicotine reduces A beta in the brain and cerebral vessels of APPsw mice.
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.
Hellström-Lindahl
Ewa
E
Karolinska Institutet, Neurotec Department, Division of Molecular Neuropharmacology, Karolinska University Hospital Huddinge B84, S-141 86 Stockholm, Sweden.
Court
Jennifer
J
Keverne
Jessica
J
Svedberg
Marie
M
Lee
Mandy
M
Marutle
Amelia
A
Thomas
Alan
A
Perry
Elaine
E
Bednar
Ivan
I
Nordberg
Agneta
A
D000367:Age Factors; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D001808:Blood Vessels / Q000187:drug effects*; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002038:Bungarotoxins / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism; D004334:Drug Administration Schedule; D004622:Embryo, Mammalian; D010450:Endopeptidases / Q000378:metabolism; D051272:Glucose Transporter Type 1; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007456:Iodine Isotopes / Q000493:pharmacokinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism; D009447:Neuroblastoma; D009538:Nicotine / Q000008:administration & dosage* / Q000494:pharmacology; D010446:Peptide Fragments / Q000032:analysis
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D019208:Brain-Derived Neurotrophic Factor; D002038:Bungarotoxins; D051272:Glucose Transporter Type 1; D007456:Iodine Isotopes; D009004:Monosaccharide Transport Proteins; D010446:Peptide Fragments; C495677:SLC2A1 protein, human; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D009538:Nicotine; D020932:Nerve Growth Factor; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C509282:Bace1 protein, mouse