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The Dose-Dependent Neuroprotective Effect of Norepinephrine in Improving Memory Retrieval in an Experimental Model of Multiple Sclerosis, Experimental Autoimmune Encephalomyelitis Publisher Pubmed



Taherian N1 ; Vaezi G1 ; Neamati A2 ; Hojjati V1 ; Ghorbanitaherdehi F3 ; Sahebkar A4, 5, 6 ; Gorjivalokola M7, 8
Authors
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Authors Affiliations
  1. 1. Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran
  2. 2. Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran
  3. 3. Department of Anatomy and Cell Biology, School of Medicine, Esfahan University of Medical Sciences, Esfahan, Iran
  4. 4. Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
  5. 5. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
  6. 6. Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
  7. 7. Department of Food and Drug Administration, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
  8. 8. Department of Pharmacology, Brain and Spinal Injury Repair Research Center, Tehran University of Medical Science, Tehran, Iran

Source: Brain Research Bulletin Published:2024


Abstract

Multiple sclerosis (MS) is considered an immune-mediated inflammatory disorder that causes cognitive impairments by damaging the hippocampal tissue. Conversely, norepinephrine (NEP) has anti-inflammatory and re-myelinating properties, which improve cognitive impairments. The aim of this study was to assess the neuroprotective effects of NEP on learning and memory disorders in an experimental animal model of MS. Two guide cannulas were bilaterally implanted in the rat hippocampal CA1 regions. After recovery, the animals received 3 μl of 0.01% ethidium bromide (EtB) in each of both hippocampal regions. After three days, the rats were randomly divided into 6 groups (8 rats/group), including control, sham 1, sham 2, and three groups of NEP 0.25, 0.5, and 1 mg/kg by intrahippocampal injection. Behavioral tests (e.g. shuttle box test and open-field test) were then performed. Finally, ROS, MDA, GSH, TNF-α, IL-6, and IL-1β concentrations in the left CA1 area, as well as using western-blot analysis, p-p38, p-JNK, p-AKT, p-ERK1/2, p-NMDA, p-AMPA, p-CREB, and BDNF proteins in the right CA1 region evaluated. The EtB injection increased ROS, MDA, TNF-α, IL-6, and IL-1β levels, as well as p-JNK and p-P38, except all other proteins, while decreasing GSH content, as well as step-through latency and locomotor activity in sham groups compared to the control group. Conversely, NEP (0.5 and 1 mg/kg, particularly at the dose of 1 mg/kg) counterbalanced all the alterations mentioned above in comparison to the sham groups. The EtB induced learning and memory impairment; however, NEP dose-dependently restored these impairments to normal levels. © 2024
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