在阿尔茨海默病小鼠模型中使用瘦素和吡格列酮进行联合治疗。

Combination treatment with leptin and pioglitazone in a mouse model of Alzheimer's disease.

作者信息

Fernandez-Martos Carmen M, Atkinson Rachel A K, Chuah Meng I, King Anna E, Vickers James C

机构信息

Wicking Dementia Research and Education Centre, Faculty of Health, University of Tasmania, Hobart, Tasmania, Australia.

出版信息

Alzheimers Dement (N Y). 2016 Dec 20;3(1):92-106. doi: 10.1016/j.trci.2016.11.002. eCollection 2017 Jan.

INTRODUCTION

Combination therapy approaches may be necessary to address the many facets of pathologic change in the brain in Alzheimer's disease (AD). The drugs leptin and pioglitazone have previously been shown individually to have neuroprotective and anti-inflammatory actions, respectively, in animal models.

METHODS

We studied the impact of combined leptin and pioglitazone treatment in 6-month-old APP/PS1 (APPswe/PSEN1dE9) transgenic AD mouse model.

RESULTS

We report that an acute 2-week treatment with combined leptin and pioglitazone resulted in a reduction of spatial memory deficits (Y maze) and brain β-amyloid levels (soluble β-amyloid and amyloid plaque burden) relative to vehicle-treated animals. Combination treatment was also associated with amelioration in plaque-associated neuritic pathology and synapse loss, and also a significantly reduced neocortical glial response.

DISCUSSION

Combination therapy with leptin and pioglitazone ameliorates pathologic changes in APP/PS1 mice and may represent a potential treatment approach for AD.