Neurotoxic effects of high-dose piperine on hippocampal synaptic transmission and synaptic plasticity in a rat model of memory impairment |
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| Affiliation: | 1. Department of Animal Sciences, School of Biological Sciences, Kharazmi University, Tehran, Iran;2. Neuroscience Research Center, Health Research Institute and Department of Physiology, School of Medicine, Babol University of Medical Sciences, Babol, Iran;3. Neuroscience Research Center, Health Research Institute and Department of Pharmacology, School of Medicine, Babol University of Medical Sciences, Babol, Iran;1. PhD Research Scholar, IKG Punjab Technical University, Kapurthala, Punjab, 144603, India;2. Department of Pharmacology, ASBASJSM College of Pharmacy, Bela, Ropar, Punjab, 140111, India;1. Department of Pharmacology, University of Zagreb School of Medicine, Salata 11, HR-10 000, Zagreb, Croatia;2. Department of Experimental Physics, Rudjer Boskovic Institute, Bijenicka 54, HR-10 000, Zagreb, Croatia;3. Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland;4. Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland;5. Zurich Center for Integrative Human Physiology, University of Zurich, Switzerland;6. Center of Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital, Würzburg, Füchsleinstrasse 15, 97080, Würzburg, Germany;7. Department of Clinical Research and Psychiatry, University of Southern Denmark Odense, Odense, Denmark;8. Research Centre of Excellence of Fundamental, Clinical and Translational Neuroscience, Croatian Institute for Brain Research, University of Zagreb School of Medicine, Salata 12, HR-10 000, Zagreb, Croatia;1. Nanobiology and Nanomedicine Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran;2. Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;3. Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran;4. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran;5. Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria;6. Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran;1. Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan;2. Laboratory for Proteolytic Neuroscience, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako, Saitama, Japan;3. Laboratory of Oncology, Pharmacy Practice and Sciences, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan;4. Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan |
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| Abstract: | In recent years, piperine has attracted much attention due to its various biological effects as a neuroprotective agent. Therefore, clarification of the possible side effects of piperine is important to identify its potential pharmacological action. Thus, the effects of piperine on the long-term plasticity of perforant pathway to dentate gyrus synapses were studied in hippocampus of an animal model of Alzheimer's disease (AD).Adult male rats were injected with intracerebroventricular (ICV) streptozotocin (STZ) bilaterally, on days 1 and 3 (3 mg/kg). The STZ-injected rats were treated with different doses of piperine for 4 weeks before being used in behavioral, electrophysiological and histopathological experiments. The passive-avoidance test was conducted on all animals in order to determine the cognitive performance. Rats were placed in a stereotaxic frame to implant a recording electrode in the hippocampal dentate gyrus and a stimulating electrode in the perforant path. Additionally, we assessed the density of survived neurons stained by cresyl violet.In this study, chronic administration of piperine low dose improved the ICV-STZ induced learning and long-term potentiation (LTP) impairments with no significant effect on baseline synaptic activity. In contrast, remarkable learning and long-term plasticity impairments were observed in rats treated by high dose of piperine in comparison to the other groups. Interestingly, this impaired hippocampal LTP was accompanied by an obvious alteration in baseline activity and significantly decreased neuronal numbers within the hippocampus. Therefore, our data provides a new understanding of the piperine supplementation effects on hippocampal electrophysiological profile although the consequences may be either beneficial or detrimental. |
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| Keywords: | Piperine Hippocampus Neurotransmission Synaptic plasticity LTP |
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