Cargando…
Agmatine Improves Cognitive Dysfunction and Prevents Cell Death in a Streptozotocin-Induced Alzheimer Rat Model
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)...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Yonsei University College of Medicine
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990080/ https://www.ncbi.nlm.nih.gov/pubmed/24719136 http://dx.doi.org/10.3349/ymj.2014.55.3.689 |
_version_ | 1782312223387942912 |
---|---|
author | Song, Juhyun Hur, Bo Eun Bokara, Kiran Kumar Yang, Wonsuk Cho, Hyun Jin Park, Kyung Ah Lee, Won Taek Lee, Kyoung Min Lee, Jong Eun |
author_facet | Song, Juhyun Hur, Bo Eun Bokara, Kiran Kumar Yang, Wonsuk Cho, Hyun Jin Park, Kyung Ah Lee, Won Taek Lee, Kyoung Min Lee, Jong Eun |
author_sort | Song, Juhyun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3990080 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Yonsei University College of Medicine |
record_format | MEDLINE/PubMed |
spelling | pubmed-39900802014-05-01 Agmatine Improves Cognitive Dysfunction and Prevents Cell Death in a Streptozotocin-Induced Alzheimer Rat Model Song, Juhyun Hur, Bo Eun Bokara, Kiran Kumar Yang, Wonsuk Cho, Hyun Jin Park, Kyung Ah Lee, Won Taek Lee, Kyoung Min Lee, Jong Eun Yonsei Med J Original Article 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. Yonsei University College of Medicine 2014-05-01 2014-04-01 /pmc/articles/PMC3990080/ /pubmed/24719136 http://dx.doi.org/10.3349/ymj.2014.55.3.689 Text en © Copyright: Yonsei University College of Medicine 2014 http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Song, Juhyun Hur, Bo Eun Bokara, Kiran Kumar Yang, Wonsuk Cho, Hyun Jin Park, Kyung Ah Lee, Won Taek Lee, Kyoung Min Lee, Jong Eun Agmatine Improves Cognitive Dysfunction and Prevents Cell Death in a Streptozotocin-Induced Alzheimer Rat Model |
title | Agmatine Improves Cognitive Dysfunction and Prevents Cell Death in a Streptozotocin-Induced Alzheimer Rat Model |
title_full | Agmatine Improves Cognitive Dysfunction and Prevents Cell Death in a Streptozotocin-Induced Alzheimer Rat Model |
title_fullStr | Agmatine Improves Cognitive Dysfunction and Prevents Cell Death in a Streptozotocin-Induced Alzheimer Rat Model |
title_full_unstemmed | Agmatine Improves Cognitive Dysfunction and Prevents Cell Death in a Streptozotocin-Induced Alzheimer Rat Model |
title_short | Agmatine Improves Cognitive Dysfunction and Prevents Cell Death in a Streptozotocin-Induced Alzheimer Rat Model |
title_sort | agmatine improves cognitive dysfunction and prevents cell death in a streptozotocin-induced alzheimer rat model |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990080/ https://www.ncbi.nlm.nih.gov/pubmed/24719136 http://dx.doi.org/10.3349/ymj.2014.55.3.689 |
work_keys_str_mv | AT songjuhyun agmatineimprovescognitivedysfunctionandpreventscelldeathinastreptozotocininducedalzheimerratmodel AT hurboeun agmatineimprovescognitivedysfunctionandpreventscelldeathinastreptozotocininducedalzheimerratmodel AT bokarakirankumar agmatineimprovescognitivedysfunctionandpreventscelldeathinastreptozotocininducedalzheimerratmodel AT yangwonsuk agmatineimprovescognitivedysfunctionandpreventscelldeathinastreptozotocininducedalzheimerratmodel AT chohyunjin agmatineimprovescognitivedysfunctionandpreventscelldeathinastreptozotocininducedalzheimerratmodel AT parkkyungah agmatineimprovescognitivedysfunctionandpreventscelldeathinastreptozotocininducedalzheimerratmodel AT leewontaek agmatineimprovescognitivedysfunctionandpreventscelldeathinastreptozotocininducedalzheimerratmodel AT leekyoungmin agmatineimprovescognitivedysfunctionandpreventscelldeathinastreptozotocininducedalzheimerratmodel AT leejongeun agmatineimprovescognitivedysfunctionandpreventscelldeathinastreptozotocininducedalzheimerratmodel |