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Galantamine increases hippocampal insulin-like growth factor 2 expression via α7 nicotinic acetylcholine receptors in mice

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Abstract

Rationale and 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 M1 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.

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Abbreviations

ACh:

Acetylcholine

ANOVA:

Analysis of variance

BDNF:

Brain-derived neurotrophic factor

CREB:

cAMP response element binding protein

FGF2:

Fibroblast growth factor 2

IGF:

Insulin-like growth factor

mAChR:

Muscarinic acetylcholine receptor

nAChR:

Nicotinic acetylcholine receptor

NGF:

Nerve growth factor

SEM:

Standard error of the mean

VEGF:

Vascular endothelial growth factor

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Acknowledgments

This study was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (from the Ministry of Education, Culture, Sports, Science and Technology of Japan).

Conflict of interest

The authors state no conflicts of interest.

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Authors and Affiliations

  1. Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Yuki Kita, Yukio Ago, Erika Takano, Asako Fukada, Kazuhiro Takuma & Toshio Matsuda

  2. United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Toshio Matsuda

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  1. Yuki Kita
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  2. Yukio Ago
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  3. Erika Takano
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  4. Asako Fukada
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  5. Kazuhiro Takuma
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  6. Toshio Matsuda
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Correspondence to Toshio Matsuda.

Additional information

Yuki Kita and Yukio Ago equally contributed to this work.

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Kita, Y., Ago, Y., Takano, E. et al. Galantamine increases hippocampal insulin-like growth factor 2 expression via α7 nicotinic acetylcholine receptors in mice. Psychopharmacology 225, 543–551 (2013). https://doi.org/10.1007/s00213-012-2841-7

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  • DOI: https://doi.org/10.1007/s00213-012-2841-7

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