Angiotensin IV possibly acts through PKMzeta in the hippocampus to regulate cognitive memory in rats |
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| Institution: | 1. Department of Pharmacology, National Defense Medical Center, Nei-Hu, 114 Taipei, Taiwan, ROC;2. Center for Neuropsychiatric Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 350, Taiwan, ROC;3. Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Nei-Hu, 114 Taipei, Taiwan, ROC;4. Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC;5. Department of Anesthesiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC;1. Departamento de Ciências Fisiológicas, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, GO, Brazil;2. Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, MG, Brazil;3. Instituto Nacional de Ciência e Tecnologia em Nanobiofarmacêutica (INCT-Nanobiofar), Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil,;1. The Core Laboratory of the First Affiliated Hospital, Lanzhou University, 1 Donggang West Road, Lanzhou 730000, China;2. Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou 730000, China;3. Institute of Biochemistry and Molecular Biology, School of Life Sciences, 222 Tianshui South Road, Lanzhou 730000, China;4. Key Laboratory of Preclinical Study for New Drugs of Gansu Province, 222 Tianshui South Road, Lanzhou 730000, China |
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| Abstract: | Ang IV is an endogenous peptide generated from the degradation of angiotensin II. Ang IV was found to enhance learning and memory in CNS. PKMzeta was identified to be a fragment of PKCzeta (protein kinase Czeta). Its continuous activation was demonstrated to be correlated with the formation of memory in the hippocampus. Therefore, we investigated whether PKMzeta participates in the effects of Ang IV on memory. We first examined the effect of Ang IV on non-spatial memory/cognition in modified object recognition test in rats. Our data showed that Ang IV could increase the exploration time on novel object. The co-administration of ZIP (PKMzeta inhibitor) with Ang IV significantly blocked the effect by Ang IV. The effects of Ang IV on hippocampal LTP at the CA1 region were also evaluated. Ang IV significantly increased the amplitude and slope of the EPSPs, which was consistent with other reports. Surprisingly, instead of potentiating LTP, Ang IV caused a failed maintenance of LTP. Moreover, there was no quantitative change in PKMzeta induced by Ang IV and/or ZIP after behavioral experiments. Taken together, our data re-confirmed the finding of the positive effect of Ang IV to enhance memory/cognition. The increased strength of EPSPs with Ang IV could also have certain functional relevance. Since the behavioral results suggested the involvement of PKMzeta, we hypothesized that the enhancement of memory/cognition by Ang IV may rely on an increase in PKMzeta activity. Overall, the present study provided important advances in our understanding of the action of Ang IV in the hippocampus. |
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