Low-dose pioglitazone can ameliorate learning and memory impairment in a mouse model of dementia by increasing LRP1 expression in the hippocampus

Hannah Seok, Minyoung Lee, Eugene Shin, Mi Ra Yun, Yong ho Lee, Jae Hoon Moon, Eosu Kim, philhyu Lee, byungwan lee, Eun Seok Kang, Hyun Chul Lee, Bong Soo Cha

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Abstract

Amyloid-β (Aβ) accumulation in the brain is a pathological feature of Alzheimer’s disease (AD) and enhancing Aβ clearance is a potential therapeutic strategy. Pioglitazone is a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist and is widely used to treat type 2 diabetes. We previously reported that low-dose pioglitazone increased the expression of low-density lipoprotein receptor-related protein 1 (LRP1), which upregulates the clearance of Aβ, using human brain microvascular endothelial cells. We investigated whether low-dose pioglitazone can rescue the pathological phenotype and memory impairment in senescence-accelerated mouse prone-8 (SAMP8) mice by increasing LRP1 levels. SAMP8 mice were treated with vehicle or pioglitazone in dosages of 2 or 5 mg/kg/day for 7 weeks. In the water maze test, 2 mg/kg/day of pioglitazone significantly attenuated the increased escape latency in SAMP8 mice (p = 0.026), while 5 mg/kg/day of treatment did not. Compared with vehicle treatment, the hippocampi of SAMP8 mice with 2 mg/kg/day of pioglitazone exhibited fewer Aβ deposits and reduced Aβ 1–40 levels, along with elevated LRP1 expression (p = 0.005). Collectively, our results proposed that a new therapeutic application of the PPAR-γ agonist for AD treatment should be considered at a lower dose than the conventional dose used to treat diabetes.

Original languageEnglish
Article number4414
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

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pioglitazone
Lipoprotein Receptors
Dementia
Hippocampus
Learning
Proteins
Peroxisome Proliferator-Activated Receptors
Alzheimer Disease
Low Density Lipoprotein Receptor-Related Protein-1
Brain
Amyloid
Type 2 Diabetes Mellitus

All Science Journal Classification (ASJC) codes

  • General

Cite this

Seok, Hannah ; Lee, Minyoung ; Shin, Eugene ; Yun, Mi Ra ; Lee, Yong ho ; Moon, Jae Hoon ; Kim, Eosu ; Lee, philhyu ; lee, byungwan ; Kang, Eun Seok ; Lee, Hyun Chul ; Cha, Bong Soo. / Low-dose pioglitazone can ameliorate learning and memory impairment in a mouse model of dementia by increasing LRP1 expression in the hippocampus. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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Low-dose pioglitazone can ameliorate learning and memory impairment in a mouse model of dementia by increasing LRP1 expression in the hippocampus. / Seok, Hannah; Lee, Minyoung; Shin, Eugene; Yun, Mi Ra; Lee, Yong ho; Moon, Jae Hoon; Kim, Eosu; Lee, philhyu; lee, byungwan; Kang, Eun Seok; Lee, Hyun Chul; Cha, Bong Soo.

In: Scientific reports, Vol. 9, No. 1, 4414, 01.12.2019.

Research output: Contribution to journalArticle

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AU - Seok, Hannah

AU - Lee, Minyoung

AU - Shin, Eugene

AU - Yun, Mi Ra

AU - Lee, Yong ho

AU - Moon, Jae Hoon

AU - Kim, Eosu

AU - Lee, philhyu

AU - lee, byungwan

AU - Kang, Eun Seok

AU - Lee, Hyun Chul

AU - Cha, Bong Soo

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