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Effect of amyloid peptides on the increase in TrkA receptor expression induced by nicotine in vitro and in vivo

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Abstract

The ability of nicotine to induce a cytoprotective or neuroprotective action occurs through several down-stream mechanisms. One possibility is that the drug increases the expression of tyrosine kinase A (TrkA) nerve growth factor (NGF) receptors. Certain β-amyloid peptides (e.g., Aβ1–42) have been shown to bind with high affinity to α7 nicotinic receptors and thus interfere with a potentially neurotrophic influence. Treatment of differentiated PC-12 cells with nicotine produced a concentration-dependent increase in cell-surface TrkA receptors that occurred concomitantly with cytoprotection. The effect of nicotine was blocked by either of the α7 receptor antagonists α-bungarotoxin (α-BTX) or methyllycaconatine. The cytoprotective action of nicotine also was inhibited by pretreatment with 10–100 nM Aβ1–42. Nicotine also was administered (four injections of 30 µg, spaced evenly over 24 h) to rats by direct injection into a lateral cerebral ventricle. Brain TrkA expression was increased significantly in hippocampus and entorhinal cortex (up to 32% above control), with no changes found in cerebral cortex or hypothalamus. The nicotine-induced increases in TrKA expression in hippocampus and entorhinal cortex were significantly inhibited by 10 µg α-BTX or by 10 nmol Aβ1–42. Therefore, physiologically relevant concentrations of Aβ1–42 can prevent nicotine-induced TrkA receptor expression in brain regions containing cholinergic neurons susceptible to the neurotoxicity associated with Alzheimer’s disease.

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Authors and Affiliations

  1. Alzheimer’s Research Center, Medical College of Georgia, Augusta, GA

    Xinyu D. Li, Ramamohana R. Jonnala, Shyamala Mruthinti & Jerry J. Buccafusco

  2. Department of Veterans Affairs Medical Center, Augusta, GA

    Shyamala Mruthinti & Jerry J. Buccafusco

  3. Departmento de Farmacologia, Instituto Teófilo Hernando, Universidad Autónoma de Madrid, Madrid, Spain

    Esperanza Arias

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  1. Xinyu D. Li
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  2. Esperanza Arias
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  3. Ramamohana R. Jonnala
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  4. Shyamala Mruthinti
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  5. Jerry J. Buccafusco
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Correspondence to Jerry J. Buccafusco.

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Li, X.D., Arias, E., Jonnala, R.R. et al. Effect of amyloid peptides on the increase in TrkA receptor expression induced by nicotine in vitro and in vivo. J Mol Neurosci 27, 325–336 (2005). https://doi.org/10.1385/JMN:27:3:325

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  • DOI: https://doi.org/10.1385/JMN:27:3:325

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