title: Atorvastatin and pitavastatin protect cerebellar Purkinje cells in AD model mice and preserve the cytokines MCP-1 and TNF-α.
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 3mg/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.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kitaku, Okayama 700-8558, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Kozuki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kurata
authors.forename: Kazunori
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Morimoto
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohta
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000069059:Atorvastatin; D018932:Chemokine CCL2 / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D011689:Purkinje Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D011758:Pyrroles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D011804:Quinolines; D014409:Tumor Necrosis Factor-alpha; D000069059:Atorvastatin; C108475:pitavastatin