The dose-dependent neuroprotective effect of norepinephrine in improving memory retrieval in an experimental model of multiple sclerosis, experimental autoimmune encephalomyelitis

Brain Res Bull. 2024 Feb 21:110907. doi: 10.1016/j.brainresbull.2024.110907. Online ahead of print.ABSTRACTMultiple 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 3μl 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 1mg/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 ...
Source: Brain Research Bulletin - Category: Neurology Authors: Source Type: research