Neuroprotective and anti-inflammatory effects of a therapy combining agonists of nicotinic α7 and σ1 receptors in a rat model of Parkinson’s disease  

作　　者：Steven Vetel Laura Foucault-Fruchard Claire Tronel Frédéric Buron Jackie Vergote Sylvie Bodard Sylvain Routier Sophie Sérrière Sylvie Chalon 

机构地区：[1]UMR 1253,iBrain,Universitéde Tours,Inserm,Tours,France [2]CHU Tours,Service pharmacie,Tours,France [3]Institut de Chimie Organique et Analytique,ICOA,UMR CNRS 7311,Universitéd’Orléans,Orléans,France

出　　处：《Neural Regeneration Research》2021年第6期1099-1104,共6页中国神经再生研究（英文版）

基　　金：supported by Inserm(to SV,LFF,CT,JV,SB,SS,SC);by the Labex IRON(ANR-11-LABX-18-01:to all authors).

摘　　要：To date there is no treatment able to stop or slow down the loss of dopaminergic neurons that characterizes Parkinson’s disease.It was recently observed in a rodent model of Alzheimer’s disease that the interaction between the α7 subtype of nicotinic acetylcholine receptor(α7-nAChR)and sigma-1 receptor(σ1-R)could exert neuroprotective effects through the modulation of neuroinflammation which is one of the key components of the pathophysiology of Parkinson’s disease.In this context,the aim of the present study was to assess the effects of the concomitant administration of N-(3R)-1-azabicyclo[2.2.2]oct-3-yl-furo[2,3-c]pyridine-5-carboxamide(PHA)543613 as an α7-nAChR agonist and 2-(4-morpholinethyl)1-phenylcyclohexanecarboxylate(PRE)-084 as aσ1-R agonist in a well-characterized 6-hydroxydopamine rat model of Parkinson’s disease.The animals received either vehicle separately or the dual therapy PHA/PRE once a day until day 14 postlesion.Although no effect was noticed in the amphetamine-induced rotation test,our data has shown that the PHA/PRE treatment induced partial protection of the dopaminergic neurons(15-20%),assessed by the dopamine transporter density in the striatum and immunoreactive tyrosine hydroxylase in the substantia nigra.Furthermore,this dual therapy reduced the degree of glial activation consecutive to the 6-hydroxydopamine lesion,i.e,the 18 kDa translocation protein density and glial fibrillary acidic protein staining in the striatum,and the CD11b and glial fibrillary acidic protein staining in the substantia nigra.Hence,this study reports for the first time that concomitant activation of α7-nAChR andσ1-R can provide a partial recovery of the nigro-striatal dopaminergic neurons through the modulation of microglial activation.The study was approved by the Regional Ethics Committee(CEEA Val de Loire n°19)validated this protocol(Authorization N°00434.02)on May 15,2014.

关 键 词：6-HYDROXYDOPAMINE astrocytes microglial activation neurodegeneration neuroinflammation nicotinicα7 receptor Parkinson’s disease PHA 543613 PRE-084 sigma-1 receptor 

分 类 号：R453[医药卫生—治疗学] R364[医药卫生—临床医学]