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

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), coronal 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

Frontiers in Aging Neuroscience, 2016, vol. 8, art. 1

Frontiers Media

Author: Santos, Sónia Sá
Santos, Sara Matos
Pinto, Antónia R T
Ramu, Vasanthakumar Ganga
Heras i Corominas, Montserrat
Bardají Rodríguez, Eduard
Tavares, Isaura R.
Castanho, Miguel Augusto Rico Botas
Date: 2016
Abstract: 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), coronal 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
Format: application/pdf
Citation: 024767
ISSN: 1663-4365
Document access: http://hdl.handle.net/10256/12445
Language: eng
Publisher: Frontiers Media
Collection: Reproducció digital del document publicat a: http://dx.doi.org/10.3389/fnagi.2016.00001
Articles publicats (D-Q)
Is part of: Frontiers in Aging Neuroscience, 2016, vol. 8, art. 1
Rights: Attribution 3.0 Spain
Rights URI: http://creativecommons.org/licenses/by/3.0/es/
Subject: Demència -- Tractament
Dementia -- Treatment
Farmacologia experimental
Experimental psychopharmacology
Title: Amidated and Ibuprofen-Conjugated Kyotorphins Promote Neuronal Rescue and Memory Recovery in Cerebral Hypoperfusion Dementia Model
Type: info:eu-repo/semantics/article
Repository: DUGiDocs

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