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

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Santos, SS (Author) Other; Santos, SM (Author) Other; Pinto, ART (Author) Other; Ramu, VG (Author) Other; Heras, M (Author) Other; Bardaji, E (Author) Other; Isaura Tavares (Author) FMUP; Castanho, MARB (Author) Other

Journal

Title: Frontiers in Aging Neuroscience

Vol. 8

ISSN: 1663-4365

Publisher: Frontiers Media

Indexing

ISI Web of Knowledge - 11 Citations

Scopus - 11 Citations

Other information

Authenticus ID: P-00K-0JH

DOI: 10.3389/fnagi.2016.00001

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11