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Agmatine improves cognitive dysfunction and prevents cell death in Streptozotocin-induced Alzheimer rat model.

Authors
 Juhyun Song  ;  Bo Eun Hur  ;  Kiran Kumar Bokara  ;  Wonsuk Yang  ;  Hyun Jin Cho  ;  Kyung Ah Park  ;  Won Taek Lee  ;  Kyoung Min Lee  ;  Jong Eun Lee 
Citation
 YONSEI MEDICAL JOURNAL, Vol.55(3) : 689-699, 2014 
Journal Title
 YONSEI MEDICAL JOURNAL 
ISSN
 0513-5796 
Issue Date
2014
MeSH
Agmatine/therapeutic use* ; Alzheimer Disease/chemically induced* ; Alzheimer Disease/drug therapy* ; Animals ; Cognition Disorders/chemically induced* ; Cognition Disorders/drug therapy* ; Disease Models, Animal ; Male ; Rats ; Streptozocin/toxicity*
Keywords
Agmatine ; Alzheimer's disease ; apoptosis ; cognitive dysfunction ; insulin signal transduction ; streptozotocin
Abstract
PURPOSE: Alzheimer's disease (AD) results in memory impairment and neuronal cell death in the brain. Previous studies demonstrated that intracerebroventricular administration of streptozotocin (STZ) induces pathological and behavioral alterations similar to those observed in AD. Agmatine (Agm) has been shown to exert neuroprotective effects in central nervous system disorders. In this study, we investigated whether Agm treatment could attenuate apoptosis and improve cognitive decline in a STZ-induced Alzheimer rat model. MATERIALS AND METHODS: We studied the effect of Agm on AD pathology using a STZ-induced Alzheimer rat model. For each experiment, rats were given anesthesia (chloral hydrate 300 mg/kg, ip), followed by a single injection of STZ (1.5 mg/kg) bilaterally into each lateral ventricle (5 μL/ventricle). Rats were injected with Agm (100 mg/kg) daily up to two weeks from the surgery day. RESULTS: Agm suppressed the accumulation of amyloid beta and enhanced insulin signal transduction in STZ-induced Alzheimer rats [experimetal control (EC) group]. Upon evaluation of cognitive function by Morris water maze testing, significant improvement of learning and memory dysfunction in the STZ-Agm group was observed compared with the EC group. Western blot results revealed significant attenuation of the protein expressions of cleaved caspase-3 and Bax, as well as increases in the protein expressions of Bcl2, PI3K, Nrf2, and γ-glutamyl cysteine synthetase, in the STZ-Agm group. CONCLUSION: Our results showed that Agm is involved in the activation of antioxidant signaling pathways and activation of insulin signal transduction. Accordingly, Agm may be a promising therapeutic agent for improving cognitive decline and attenuating apoptosis in AD.
Files in This Item:
T201400842.pdf Download
DOI
10.3349/ymj.2014.55.3.689
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Park, Kyung Ah(박경아)
Song, Ju Hyun(송주현)
Lee, Won Taek(이원택) ORCID logo https://orcid.org/0000-0001-7348-9562
Lee, Jong Eun(이종은) ORCID logo https://orcid.org/0000-0001-6203-7413
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/98408
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