Amidated and Ibuprofen-Conjugated Kyotorphins Promote Neuronal Rescue and Memory Recovery in Cerebral Hypoperfusion Dementia Model

被引：12

作者：

Santos, Sonia Sa ^{[1
]}

Santos, Sara M. ^{[1
]}

Pinto, Antonia R. T. ^{[1
]}

Ramu, Vasanthakumar G. ^{[2
]}

Heras, Montserrat ^{[2
]}

Bardaji, Eduard ^{[2
]}

Tavares, Isaura ^{[3
,4
,5
]}

Castanho, Miguel A. R. B. ^{[1
]}

机构：

[1] Fac Med Lisbon, Inst Med Mol, Lisbon, Portugal

[2] Univ Girona, Dept Quim, Lab Innovacio Proc & Prod Sintesi Organ, Girona, Spain

[3] Fac Med Porto, Dept Biol Expt, Oporto, Portugal

[4] Inst Biol Mol & Celular, Oporto, Portugal

[5] Univ Porto, Inst Inovacao & Invest Saude i3S, Rua Campo Alegre 823, P-4100 Oporto, Portugal

来源：

FRONTIERS IN AGING NEUROSCIENCE | 2016年 / 8卷

关键词：

2VO-dementia model; chronic cerebral hypoperfusion; cognitive impairment; hippocampus; kyotorphin derivatives; neuroprotection; MET-ENKEPHALIN RELEASER; TYROSYL-L-ARGININE; ALZHEIMERS-DISEASE; SPATIAL MEMORY; HIPPOCAMPAL CA1; DENTATE GYRUS; NITRIC-OXIDE; BOVINE BRAIN; RAT; IMPAIRMENT;

D O I：

10.3389/fnagi.2016.00001

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

Chronic brain ischemia is a prominent risk factor for neurological dysfunction and progression for dementias, including Alzheimer's disease (AD). In rats, permanent bilateral common carotid artery occlusion (2VO) causes a progressive neurodegeneration in the hippocampus, learning deficits and memory loss as it occurs in AD. Kyotorphin (KTP) is an endogenous antinociceptive dipeptide whose role as neuromodulator/neuroprotector has been suggested. Recently, we designed two analgesic KTP-derivatives, KTP-amide (KTP-NH2) and KTP-NH2 linked to ibuprofen (IbKTP-NH2) to improve KTP brain targeting. This study investigated the effects of KTP-derivatives on cognitive/behavioral functions (motor/spatial memory/nociception) and hippocampal pathology of female rats in chronic cerebral hypoperfusion (2VO-rat model). 2VO-animals were treated with KTP-NH2 or IbKTP-NH2 for 7 days at weeks 2 and 5 post-surgery. After behavioral testing (week 6), corona' sections of hippocampus were H&E-stained or immunolabeled for the cellular markers GFAP (astrocytes) and NFL (neurons). Our findings show that KTP-derivatives, mainly IbKTP-NH2, enhanced cognitive impairment of 2VO-animals and prevented neuronal damage in hippocampal CA1 subfield, suggesting their potential usefulness for the treatment of dementia.

引用

页数：11

共 49 条

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