ABSTRACT
Diabetes mellitus often results in a number of complications involving impaired brain function, including cognitive deficits and depression. However, the potential mechanisms for diabetes-related cognitive deficits and depression are not fully understood. Neurons in the hippocampal, cortical and amygdala functional regions are more susceptible to damage during hyperglycemia. Neuroprotection in the brain can rescue cognitive deficits and depression induced by hyperglycemia. This study investigated the potential mechanisms underlying diabetes-related congnitive deficits and depression, determined whether the inflammatory factor inducible nitric oxide synthase (iNOS) and the nitric oxide (NO)/soluble guanylyl cyclases (sGC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) pathway, play key roles in cognitive deficits and depression associated. In the present study, diabetic animal models were induced by streptozotocin (STZ, 150mg/kg) in mice, and aminoguanidine (AG), a selective inhibitor of iNOS, was given by intraperitoneal injection for 10 weeks. Blood glucose, activities of NOS and the levels of NO in serum and brain regions were measured. The spatial memory was detected using the Morris water maze test, depressive behavior was evaluated by the tail suspension test (TST), forced swimming test (FST), closed field test (CFT) and open field test (OFT). We also detected neuronal survival and cleaved caspase-3 positive ratios in three brain regions and the levels of iNOS, sGC, cGMP and PKG in hippocampus and frontal cortex. Data indicated that diabetic mice exerted impairments in spatial memory, decreased locomotor activity and increased immobile time in diabetic mice. In addition, diabetic mice had significantly decreased surviving neuronal density and showed signs of obvious neuronal injury in the hippocampus, frontal cortex and amygdala. iNOS overexpression and its associated signaling pathway NO/sGC/cGMP/PKG in the hippocampus and frontal cortex were implicated during hyperglycemia. However, AG improved the behavior disorders, reduced the activity of iNOS, protected nerve cells and inhibited the level of iNOS, sGC, PKG and cleaved caspase-3 in the hippocampus and cortex. These results suggested that iNOS/NO/sGC/cGMP/PKG signal pathway is a key feature of cognitive deficits and depression associated with diabetes. AG ameliorated cognitive deficits and depression in diabetic mice by exerting anti-inflammatory and neuroprotective effects by suppressing iNOS-associated signaling pathways.
Subject(s)
Cognition Disorders/drug therapy , Depressive Disorder/drug therapy , Diabetes Complications/drug therapy , Diabetes Mellitus, Experimental/drug therapy , Nitric Oxide Synthase Type II/antagonists & inhibitors , Psychotropic Drugs/pharmacology , Animals , Brain/drug effects , Brain/enzymology , Brain/pathology , Cognition Disorders/complications , Cognition Disorders/enzymology , Cognition Disorders/psychology , Depressive Disorder/complications , Depressive Disorder/enzymology , Depressive Disorder/psychology , Diabetes Complications/enzymology , Diabetes Complications/psychology , Diabetes Mellitus, Experimental/enzymology , Diabetes Mellitus, Experimental/psychology , Enzyme Inhibitors/pharmacology , Guanidines/pharmacology , Hypoglycemic Agents/pharmacology , Male , Mice, Inbred ICR , Nitric Oxide Synthase Type II/metabolism , Signal Transduction/drug effectsABSTRACT
The ecological environment of semi-arid regions in China is fragile, and the situation of protecting environment is grim. So it is urgent to strengthen environment protection and ecological construction in semi-arid region. Four different vegetation ecosystems were selected in semi-arid region with Wuchuan County in Inner Mongolia as a case study: the bushes, the trees, the alfalfa land, and artificially mixed sowing grassland. The soil was sampled and carried to laboratory for analysis of the content of lead, cadmium and chromium in the soil in May and September (the start of the growing season and the end of the growing season). It was showed that among the four different ecosystems, the lead and cadmium contents in the soil were significantly different in variability, while the chromium is not significant. And the changing rate trend of the content of lead and cadmium is consistent: the contents of the both elements in May are higher than in September obviously. The degree of the order of the content change is also very close. The biggest of the change scope is from the bushes and artificially mixed sowing grassland, followed by the alfalfa land, and finally the trees. Therefore, it is more favorable to plant shrubs and grass for absorbing heavy metals in the soil in the common local vegetation eco-system.
Subject(s)
Ecosystem , Metals, Heavy/analysis , Soil/chemistry , China , Conservation of Natural Resources , Desert Climate , Medicago sativa , Poaceae , Seasons , TreesABSTRACT
OBJECTIVE: To observe the pathological change in the brain of Angiostrongylus cantonensis-infected mouse. METHODS: Forty-eight mice were orally infected each with 40 third stage larvae of A. cantonensis, 3 mice were sacrificed at 7, 10, 13, 16, 19, 22, 25, 28 days postinfection respectively for worm recovery, and another 3 mice were for observing the histopathological change in tissue sections of the brain. RESULTS: Ten days postinfection, worms were found in the brain of the infected mice with a mean worm number of (7.0+/-1.7) per mouse. The highest number of worms was found at 16 days postinfection, with a mean of (23.7+/-4.9) per mouse. Notable symptoms of nervous system were seen on 15 days postinfection. Most mice died around 22 days postinfection. Histological examination revealed mechanical damages. Cavities and inflammation were observed in the brain parenchyma. Worms were seen in the subarachnoid space. Meningitis-like signs started at 13 days and aggravated then. CONCLUSIONS: Infection of A. cantonensis causes pathological change in mouse brain and the process is aggravating with postinfection time.
