Atorvastatin and pitavastatin reduce oxidative stress and improve IR/LDL-R signals in alzheimer's disease

Tomoko Kurata, Kazunori Miyazaki, Nobutoshi Morimoto, Hiromi Kawai, Yasuyuki Ohta, Yoshio Ikeda, Koji Abe

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Objectives: To examine and compare the pleiotropic effects on oxidative stress and metabolic signaling pathways of atorvastatin and pitavastatin in mouse model of Alzheimer's disease (AD). Methods: We gave the transgenic (Tg) mice either atorvastatin or pitavastatin from 5-20 months (M) of age, and performed immunohistological analysis [4-hydroxy-2-nonenal (4-HNE)-positive, advanced glycation end products (AGEs), low-density lipoprotein receptor (LDL-R)-positive neurons, apolipoprotein E (ApoE)- positive senile plaque (SP), and insulin receptor (IR)-positive endothelium], and biochemistry analysis (adiponectin and leptin). Results: The numbers of 4-HNE- and AGE-positive neurons and the sum of ApoE-positive SP size progressively increased with age in amyloid precursor protein (APP)-Tg mice, while the amount of IR- positive endothelium and the number of LDL-R-positive neurons decreased. Adiponectin and leptin serum levels were lower in APP-Tg mice than in non-Tg mice. Treatment with statins reduced the number of AGE- positive neurons from as early as 10 M, preserved the numbers of 4-HNE- and LDL-R-positive neurons and the amount of IR-positive endothelium at 15 M, and reduced the sum of ApoE-positive SP size and adiponectin serum level at 20 M. Discussion: Atorvastatin and pitavastatin reduced the level of oxidative stress, as revealed by the presence of 4-HNE and AGE, in AD mouse brains, and that treatment with statins improves insulin signaling and LDL- R/ApoE systems. The beneficial effects of these statins may be associated with direct pleiotropic effects on AD mouse brains, indirect effects through improving the serum adiponectin/leptin balance, or both.

Original languageEnglish
Pages (from-to)193-205
Number of pages13
JournalNeurological Research
Volume35
Issue number2
DOIs
Publication statusPublished - 2013

Fingerprint

LDL Receptors
Insulin Receptor
Adiponectin
Apolipoproteins E
Alzheimer Disease
Oxidative Stress
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Amyloid Plaques
Neurons
Leptin
Transgenic Mice
Endothelium
Amyloid beta-Protein Precursor
Serum
Advanced Glycosylation End Products
Brain
Metabolic Networks and Pathways
Biochemistry
Atorvastatin Calcium
pitavastatin

Keywords

  • Alzheimer's disease
  • Atorvastatin
  • Insulin receptor
  • LDL receptor
  • Pitavastatin

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Medicine(all)

Cite this

Atorvastatin and pitavastatin reduce oxidative stress and improve IR/LDL-R signals in alzheimer's disease. / Kurata, Tomoko; Miyazaki, Kazunori; Morimoto, Nobutoshi; Kawai, Hiromi; Ohta, Yasuyuki; Ikeda, Yoshio; Abe, Koji.

In: Neurological Research, Vol. 35, No. 2, 2013, p. 193-205.

Research output: Contribution to journalArticle

Kurata, Tomoko ; Miyazaki, Kazunori ; Morimoto, Nobutoshi ; Kawai, Hiromi ; Ohta, Yasuyuki ; Ikeda, Yoshio ; Abe, Koji. / Atorvastatin and pitavastatin reduce oxidative stress and improve IR/LDL-R signals in alzheimer's disease. In: Neurological Research. 2013 ; Vol. 35, No. 2. pp. 193-205.
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T1 - Atorvastatin and pitavastatin reduce oxidative stress and improve IR/LDL-R signals in alzheimer's disease

AU - Kurata, Tomoko

AU - Miyazaki, Kazunori

AU - Morimoto, Nobutoshi

AU - Kawai, Hiromi

AU - Ohta, Yasuyuki

AU - Ikeda, Yoshio

AU - Abe, Koji

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AB - Objectives: To examine and compare the pleiotropic effects on oxidative stress and metabolic signaling pathways of atorvastatin and pitavastatin in mouse model of Alzheimer's disease (AD). Methods: We gave the transgenic (Tg) mice either atorvastatin or pitavastatin from 5-20 months (M) of age, and performed immunohistological analysis [4-hydroxy-2-nonenal (4-HNE)-positive, advanced glycation end products (AGEs), low-density lipoprotein receptor (LDL-R)-positive neurons, apolipoprotein E (ApoE)- positive senile plaque (SP), and insulin receptor (IR)-positive endothelium], and biochemistry analysis (adiponectin and leptin). Results: The numbers of 4-HNE- and AGE-positive neurons and the sum of ApoE-positive SP size progressively increased with age in amyloid precursor protein (APP)-Tg mice, while the amount of IR- positive endothelium and the number of LDL-R-positive neurons decreased. Adiponectin and leptin serum levels were lower in APP-Tg mice than in non-Tg mice. Treatment with statins reduced the number of AGE- positive neurons from as early as 10 M, preserved the numbers of 4-HNE- and LDL-R-positive neurons and the amount of IR-positive endothelium at 15 M, and reduced the sum of ApoE-positive SP size and adiponectin serum level at 20 M. Discussion: Atorvastatin and pitavastatin reduced the level of oxidative stress, as revealed by the presence of 4-HNE and AGE, in AD mouse brains, and that treatment with statins improves insulin signaling and LDL- R/ApoE systems. The beneficial effects of these statins may be associated with direct pleiotropic effects on AD mouse brains, indirect effects through improving the serum adiponectin/leptin balance, or both.

KW - Alzheimer's disease

KW - Atorvastatin

KW - Insulin receptor

KW - LDL receptor

KW - Pitavastatin

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