PPARγ agonists regulate bidirectional transport of amyloid‐β across the blood–brain barrier and hippocampus plasticity in db/db mice

• DOI: 10.1111/bph.13378
• Publication Date: 2015-10-28T05:43:16Z
• Authors: Hao Wang; Fang Chen; Kai Long Zhong; Su Su Tang; Mei Hu; Yan Long; Ming Xing Miao; Jian Min Liao; Hong Bing Sun; Hao Hong
• Keywords: LRP1; RAGE

Background and Purpose There is emerging evidence suggesting that abnormal transport of amyloid‐β (Aβ) across the blood–brain barrier (BBB) involved in diabetes‐associated cognitive decline. We investigated whether PPARγ agonists restore Aβ BBB hippocampal plasticity db / mice. Experimental Approach Efflux influx were determined by stereotaxic intra‐cerebral or i.a. infusion [ 125 I]‐Aβ 1–40 respectively. Receptor for advanced glycation end products (RAGE) low‐density lipoprotein receptor‐related protein 1 (LRP1), which are efflux, NF‐κB p65 at BBB, as well Aβ, caspase‐3, Bax Bcl‐2 assayed Western blot, immunohistochemistry RT‐PCR. In vivo , LTP was recorded, Morris water maze Y‐maze tasks performed. Key Results Treatment with agonists, rosiglitazone (0.8 mg·kg −1 ) pioglitazone (9.0 ), 6 weeks significantly increased efflux decreased Concomitantly, they 1–42 suppressed neuronal apoptosis, indicated caspase‐3 activity ratio Bcl‐2/Bax, plasticity, characterized an enhanced better performance behavioural tests. Furthermore, induced expression LRP1 gene activation RAGE inactivation signalling Conclusions Implications modify this accompanied amelioration β‐amyloidosis improvement diabetic