Agmatine improves cognitive dysfunction and prevents cell death in a streptozotocin-induced Alzheimer rat model.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea.
Juhyun
J
Song
Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea. ; Brain Korea 21 Plus Project for Medical Science, Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
Bo Eun
BE
Hur
Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea.
Kiran Kumar
KK
Bokara
Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea.
Wonsuk
W
Yang
Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea.
Hyun Jin
HJ
Cho
Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea.
Kyung Ah
KA
Park
Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea.
Won Taek
WT
Lee
Department of Neurology, Seoul National University College of Medicine, Seoul, Korea.
Kyoung Min
KM
Lee
Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea. ; Brain Korea 21 Plus Project for Medical Science, Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
Jong Eun
JE
Lee
D000376:Agmatine / Q000627:therapeutic use*; D000544:Alzheimer Disease / Q000139:chemically induced* / Q000188:drug therapy*; D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D004195:Disease Models, Animal; D008297:Male; D051381:Rats; D013311:Streptozocin / Q000633:toxicity*
D013311:Streptozocin; D000376:Agmatine
Agmatine; Alzheimer's disease; apoptosis; cognitive dysfunction; insulin signal transduction; streptozotocin