title: Galantamine increases hippocampal insulin-like growth factor 2 expression via α7 nicotinic acetylcholine receptors in mice.
abstract: OBJECTIVE
  Galantamine, a drug for the treatment of Alzheimer's disease, has neuroprotection in several experimental models and stimulates adult neurogenesis in the rodent brain, but the exact mechanism remains unclear. This study examined whether galantamine affects the expression of neurotrophic/growth factors in the mouse hippocampus and prefrontal cortex.
  
  
  METHODS
  Nine-week-old male ddY mice were used. The mRNA levels of neurotrophic/growth factors were analyzed by a real-time quantitative PCR. The protein levels of insulin-like growth factor 2 (IGF2) were analyzed by Western blotting.
  
  
  RESULTS
  Acute administration of galantamine (0.3-3 mg/kg, i.p.) increased IGF2 mRNA levels in the hippocampus, but not in the prefrontal cortex, in time- and dose-dependent manner. Galantamine (3 mg/kg, i.p.) caused a transient increase in fibroblast growth factor 2 mRNA levels and a decrease in brain-derived neurotrophic factor mRNA levels in the hippocampus, while it did not affect the mRNA levels of other neurotrophic/growth factors. The galantamine-induced increase in the hippocampal IGF2 mRNA levels was blocked by mecamylamine, a nonselective nicotinic acetylcholine (ACh) receptor (nAChR) antagonist, and methyllycaconitine, a selective α7 nAChR antagonist, but not by telenzepine, a preferential M(1) muscarinic ACh receptor antagonist. Moreover, the selective α7 nAChR agonist PHA-543613 increased the IGF2 mRNA levels, while donepezil, an acetylcholinesterase inhibitor, did not. Galantamine also increased hippocampal IGF2 protein, which was blocked by methyllycaconitine.
  
  
  CONCLUSIONS
  These findings suggest that galantamine increases hippocampal IGF2 levels via α7 nAChR activation in mice and imply that the effect may contribute to its neuroprotection or neurogenesis.
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kita
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ago
authors.forename: Erika
authors.initials: E
authors.lastname: Takano
authors.forename: Asako
authors.initials: A
authors.lastname: Fukada
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takuma
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D005702:Galantamine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013997:Time Factors; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579166:Chrna7 protein, mouse; C513121:IGF2 protein, mouse; D018696:Neuroprotective Agents; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005702:Galantamine; D007335:Insulin-Like Growth Factor II