UPREGULATED EXPRESSION OF BRAIN ENZYMATIC MARKERS OF ARACHIDONIC AND DOCOSAHEXAENOIC ACID METABOLISM IN A RAT MODEL OF THE METABOLIC SYNDROME. BACKGROUND: In animal models, the metabolic syndrome elicits a cerebral response characterized by altered phospholipid and unesterified fatty acid concentrations and increases in pro-apoptotic inflammatory mediators that may cause synaptic loss and cognitive impairment. We hypothesized that these changes are associated with disturbed metabolism of phospholipase (PLA2) enzymes that regulate arachidonic (AA, 20:4n-6) and docosahexaenoic (DHA, 22:6n-6) acid metabolism, in brain. Male Wistar rats were fed a control or high-sucrose diet for 8 weeks to produce the metabolic syndrome. Thus diet induced insulin resistance, and increased phosphorylated-cPLA2 protein, cPLA2 and iPLA2 activity and 12-lipoxygenase mRNA, but decreased BDNF mRNA and protein, and drebrin mRNA, concentrations of several n-6 fatty acids These findings show upregulated brain AA and DHA metabolism and reduced BDNF and drebrin, in an animal model of the metabolic syndrome, all of which may contribute to functional impairment. LOW-DOSE ASPIRIN DAMPENS INFLAMMATION-INDUCED INCREMENTS IN BRAIN ARACHIDONIC ACID METABOLITES IN OLD HIV-1 TRANSGENIC RAT. HIV-1 transgenic rats develop behavioral changes with aging and show neuroinflammation, neuronal loss, and increased brain arachidonic acid (AA) metabolism. They may be a model for HAND. We reported that chronic low-dose aspirin (equivalent to a human low dose) reduced upregulated brain AA metabolism in aged HIV-1 transgenic rats. Wildtype and HIV-1 transgenic rats, aged 7-9 months, were treated for 42 days with 10 mg/kg/day (equivalent to human low-dose) aspirin in drinking water, then were subjected to head-focused microwave fixation. Enzyme-linked immunosorbent assays showed that brain 15-epi-lipoxin A4 and 8-isoprostane concentrations were significantly higher in the HIV-1 transgenic rats. These differences were insignificant following aspirin. Aspirin also reduced brain prostaglandin E2 and leukotriene B4 concentrations in HIV-1 Tg but not wildtype rats. Thromboxane B2, 15-HETE, lipoxin A4 and resolvin D1 concentrations were unrelated to genotype or treatment. Thus, treatment with low-dose aspirin reduces AA-metabolite markers of inflammation and oxidative stress in HIV-1 Tg brain, and might be considered in clinical trials in HIV-1 patients with HAND. ADOLESCENT BEHAVIOR AND DOPAMINE AVAILABILITY ARE SENSITIVE TO DIETARY N-3 FATTY ACID CONTENT. Understanding environmental factors that contribute to behavioral health is critical for successful prevention strategies in individuals at risk for psychiatric disorders. Dietary deficiency of N-3 polyunsaturated fatty acids (PUFAs) has been implicated in schizophrenia and mood disorders, which typically occur during adolescence to early adulthood. Thus, adolescence might be the critical age range for the negative impact of diet as an environmental insult. A rat model involving consecutive generations of n-3 PUFA deficiency was developed on the assumption that dietary trends toward decreased consumption of these PUFAS began 4-5 decades ago when parents of current adolescents were born. Behavioral performance in a range of tasks as well as markers of dopamine-related neurotransmission were compared in adolescents and adult rats fed n-3 PUFA adequate and deficient diets. In adolescents, n-3 PUFA deficiency across consecutive generations produced a modality-selective and task-dependent impairment in cognitive and motivated behavior distinct from the deficits observed in adults. Although this dietary deficiency affected expression of dopamine-related proteins in both age groups in adolescents but not adults, there was an increase in tyrosine hydroxylase expression that was selective to the dorsal striatum. These data support a nutritional contribution to optimal cognitive and affective functioning in adolescents.
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