ABSTRACT
<p><b>OBJECTIVE</b>To investigate the protective effects of docosahexaenoic acid (DHA) and nervonic acid (NA) on the learning and memory abilities in rats exposed to 1-bromopropane (1-BP) and their action mechanisms.</p><p><b>METHODS</b>Forty male Wistar rats (specific pathogen-free) were randomly divided into 4 groups (n = 10 for each), i.e., solvent control group, 1-BP (800 mg/kg) group, NA (150 mg/kg) + 1-BP (800 mg/kg) group, and DHA (500 mg/kg) + 1-BP (800 mg/kg) group. The rats were given respective test substances by gavage for 7 d. The Morris water maze (MWM) test was performed from days 8 to 12 to evaluate the rats' learning and memory abilities. After MWM test, rats were sacrificed in the next day, and cerebral cortex was quickly dissected and homogenized in an ice bath. The supernatant of the obtained homogenate was collected to measure the content of glutathione (GSH) and malondialdehyde (MDA) and the activities of glutathione reductase (GR) and γ-glutamate cysteine ligase (γ-GCL).</p><p><b>RESULTS</b>The MWM spatial navigation test showed that the 1-BP group had significantly longer escape latency and significantly longer total swimming distance compared with the control group (P<0.05), while the DHA+1-BP group had significant decreases in escape latency and total swimming distance compared with the 1-BP group (P<0.05). The spatial probe test showed that the number of platform crossings was significantly greater in the DHA+1-BP group and NA+1-BP group than in the 1-BP group (P<0.05); compared with the control group, the 1-BP group had a significantly lower ratio of time spent in the zone around the platform to total time (P < 0.05), and the ratio was significantly higher in the DHA+1-BP group than in the 1-BP group (P < 0.05). Compared with the control group, the 1-BP group had a 18.1% decrease in GSH content, and DHA could significantly reverse 1-BP-induced decrease in GSH content (P < 0.05). Compared with the 1-BP group, the DHA+1-BP group and NA+1-BP group had significantly decreased MDA content (P < 0.05), the DHA+1-BP group had significantly increased GR activity (P < 0.05), and the NA+1-BP group had significantly increased γ-GCL activity (P < 0.05).</p><p><b>CONCLUSION</b>The rats exposed to 1-BP have oxidative stress in the brain and impaired cognitive function. DHA and NA can reduce 1-BP-induced cognitive function impairment in rats, possibly by increasing the activities of GR and γ-GCL and the content of GSH in the brain.</p>
Subject(s)
Animals , Male , Rats , Behavior, Animal , Brain , Docosahexaenoic Acids , Pharmacology , Fatty Acids, Monounsaturated , Pharmacology , Glutamate-Cysteine Ligase , Metabolism , Glutathione , Metabolism , Glutathione Reductase , Metabolism , Hydrocarbons, Brominated , Toxicity , Malondialdehyde , Metabolism , Maze Learning , Memory , Oxidative Stress , Rats, WistarABSTRACT
<p><b>OBJECTIVE</b>To investigate the role of T cell and its subsets in the induction of insulitis and type 1 diabetes mellitus (T1DM) in BALB/c mice.</p><p><b>METHODS</b>Autoimmune diabetes mellitus was developed by intraperitoneal injection of 40 mg/kg streptozotocin (STZ) daily for 5 consecutive days in BALB/c mice as sources of donor cells. Spleen cells from diabetic mice were then cultured for 7 days in the stimulation of interleukin-2 (IL-2) to harvest diabetogenic T cells, which were subsequently transferred into normal BALB/c mice recipients. MTT, ELISA, and HE staining were used to analyze the lymphocyte proliferation, cytokine (IL-2, interferon-gamma, IL-4, and IL-10) levels, and pathological changes in pancreatic islets.</p><p><b>RESULTS</b>As few as 3 x 10(6) diabetogenic T cells successfully induced diabetes mellitus in recipients pretreated with STZ twice, whereas transfer of equal amount of normal splenocytes, T cell-depleted diabetogenic splenocytes, or diabetogenic CD4+ T cells alone in recipients receiving STZ twice pretreatment was proved not to induce diabetes mellitus either. A markedly increased lymphocyte proliferation, high levels of interferon-gamma and IL-2 in the supernatants of diabetogenic T cells were observed. In addition, a markedly enhanced lymphocyte proliferation, a high level of interferon-gamma secretion in serum, and numerous lymphocytes infiltration in pancreatic islets were detected in the diabetic mice induced by diabetogenic T cells transfer.</p><p><b>CONCLUSIONS</b>A novel T1DM murine model is established in STZ-pretreated BALB/c mice by adoptive transfer of diabetogenic T cells. CD4+ T cells with interferon-gamma may promote the onset of diabetes mellitus.</p>