Occupational-like organophosphate exposure disrupts microglia and accelerates deficits in a rat model of Alzheimer’s disease

Male TgF344-AD rats are selectively susceptible to accelerated learning deficits as a function of CPF exposure at 6 months of age. a, b Locomotor activity is not significantly affected by CPF treatment or genotype in males or females at 6 months of age. Open-field treatment effect: male F1,52？=？1.496, P？=？.2268; female F1,53？=？1.425, P？=？0.2379. Open-field genotype effect: male F1,52？=？0.3095, P？=？0.5804; female F1,53？=？5.669, P？=？0.0209. c–h Acquisition of learning and memory deficits in two different tasks is observed in male TgF344-AD CPF-exposed rats, while WT males are unaffected. Female rats of either genotype or exposure group also perform normally in tasks of learning and memory at 6 months of age. For each task, the diagrams on the right indicate the relationship of the magnitude of the measured parameter to quality of performance on the task. c TgF344-AD CPF-exposed males display lower preference for the novel object in the NOR task than WT littermates, while there is no statistically significant difference between TgF344-AD and WT male rats in the vehicle group. NOR treatment effect for males was F1,74？=？3.766, P？=？0.0561, while NOR genotype effect was F1,74？=？7.222, P？=？0.0089. d No deficits in females from any group were seen in NOR. NOR treatment effect for females was F 1,69？=？0.001374, P？=？0.9705, while the NOR genotype effect was F 1,69？=？0.2664, P？=？0.6074. e, f Male CPF-exposed TgF344-AD rats make more errors in BM reversal learning, while female CPF-exposed TgF344-AD rats do not. BM reversal learning treatment effect: male F1,86？=？3.317, P？=？0.0720; female F1,86？=？4.576, P？=？0.0353. BM reversal learning genotype effect: male F1,86？=？5.972, P？=？0.0166; female F1,86？=？0.6869, P？=？0.4095. g Male CPF-exposed TgF344-AD rats spend less time at the escape hole location in the probe test of the BM reversal and h make more errors in locating the target in the memory probe phase of the test. No significant impairments in behavior after CPF exposure are observed in females regardless of genotype. BM reversal memory probe treatment effect on time spent at escape: male F1,82？=？10.04, P？=？0.0022; female F1,88？=？2.083, P？=？0.1525. BM reversal memory probe genotype effect on time spent at escape: male F1,82？=？3.205, P？=？0.0771; female F1,88？=？0.0657, P？=？0.7984. BM reversal memory probe treatment effect on percent correct nose pokes: male F1,82？=？4.780, P？=？0.0317; female F1,86？=？0.0081, P？=？0.9283. BM reversal memory probe genotype effect on percent correct nose pokes: male F1,82？=？5.296, P？=？0.0243; female F1,86？=？1.236, P？=？0.2694. For each task,