Atorvastatin and pitavastatin protect cerebellar Purkinje cells in AD model mice and preserve the cytokines MCP-1 and TNF-α

Miki Kozuki, Tomoko Kurata, Kazunori Miyazaki, Nobutoshi Morimoto, Yasuyuki Ohta, Yoshio Ikeda, Koji Abe

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

In contrast to cerebral cortical neurons, the extent of damage to cells of the cerebellum in Alzheimer's disease (AD) is still a matter of debate. Here, we examined pathological changes in the cerebellar Purkinje cells (PCs) of AD model mice (amyloid precursor protein transgenic (APP-Tg) mice) at 10, 15, and 20 months (M) of age, and investigated the possible protective effect of two strong statins (atorvastatin at 30 mg/kg/day or pitavastatin at 3 mg/kg/day, p.o.) by administering these statins from 5 to 20 M. The number of PCs detected by hematoxylin-eosin staining in APP-Tg mice was approximately 60% of the number in non-Tg mice at 10 M, and this progressively reduced with age until 20 M. Moreover, the number of monocyte chemotactic protein 1 (MCP-1)-positive PCs and tumor necrosis factor alpha (TNF-α)-positive PCs was also reduced in the transgenics. In contrast, the APP-Tg mice treated with either of the two statins showed a significant recovery in the number of PCs, and MCP-1 (at 20 M) and TNF-α (at 15 and 20 M) staining in PCs was preserved. Because MCP-1 and TNF-α play important roles in maintaining the synaptic network in PCs, the present study suggests that atorvastatin and pitavastatin can maintain the number of PCs and their synaptic networks in the AD cerebellum.

Original languageEnglish
Pages (from-to)32-38
Number of pages7
JournalBrain Research
Volume1388
DOIs
Publication statusPublished - May 4 2011

Fingerprint

Chemokine CCL2
Purkinje Cells
Alzheimer Disease
Tumor Necrosis Factor-alpha
Cytokines
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Amyloid beta-Protein Precursor
Transgenic Mice
Cerebellum
Staining and Labeling
Atorvastatin Calcium
pitavastatin
Hematoxylin
Eosine Yellowish-(YS)
Neurons

Keywords

  • Alzheimer's disease
  • Atorvastatin
  • Cerebellum
  • Pitavastatin
  • Purkinje cell

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Atorvastatin and pitavastatin protect cerebellar Purkinje cells in AD model mice and preserve the cytokines MCP-1 and TNF-α. / Kozuki, Miki; Kurata, Tomoko; Miyazaki, Kazunori; Morimoto, Nobutoshi; Ohta, Yasuyuki; Ikeda, Yoshio; Abe, Koji.

In: Brain Research, Vol. 1388, 04.05.2011, p. 32-38.

Research output: Contribution to journalArticle

Kozuki, Miki ; Kurata, Tomoko ; Miyazaki, Kazunori ; Morimoto, Nobutoshi ; Ohta, Yasuyuki ; Ikeda, Yoshio ; Abe, Koji. / Atorvastatin and pitavastatin protect cerebellar Purkinje cells in AD model mice and preserve the cytokines MCP-1 and TNF-α. In: Brain Research. 2011 ; Vol. 1388. pp. 32-38.
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AB - In contrast to cerebral cortical neurons, the extent of damage to cells of the cerebellum in Alzheimer's disease (AD) is still a matter of debate. Here, we examined pathological changes in the cerebellar Purkinje cells (PCs) of AD model mice (amyloid precursor protein transgenic (APP-Tg) mice) at 10, 15, and 20 months (M) of age, and investigated the possible protective effect of two strong statins (atorvastatin at 30 mg/kg/day or pitavastatin at 3 mg/kg/day, p.o.) by administering these statins from 5 to 20 M. The number of PCs detected by hematoxylin-eosin staining in APP-Tg mice was approximately 60% of the number in non-Tg mice at 10 M, and this progressively reduced with age until 20 M. Moreover, the number of monocyte chemotactic protein 1 (MCP-1)-positive PCs and tumor necrosis factor alpha (TNF-α)-positive PCs was also reduced in the transgenics. In contrast, the APP-Tg mice treated with either of the two statins showed a significant recovery in the number of PCs, and MCP-1 (at 20 M) and TNF-α (at 15 and 20 M) staining in PCs was preserved. Because MCP-1 and TNF-α play important roles in maintaining the synaptic network in PCs, the present study suggests that atorvastatin and pitavastatin can maintain the number of PCs and their synaptic networks in the AD cerebellum.

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