Brain research
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Previous work showed that sleep deprivation (SD) impairs hippocampal-dependent cognitive function and synaptic plasticity, and a novel wake-promoting agent modafinil prevents SD-induced memory impairment in rat. However, the mechanisms by which modafinil prevented REM-SD-induced impairment of brain function remain poorly understood. In the present study, rats were sleep-deprived by using the modified multiple platform method and brain function was detected. ⋯ A synaptic plasticity-related gene, MMP-9 expression was also upregulated in modafinil-treated rats. Importantly, downregulation of MMP-9 expression by special siRNA decreased synapsin I protein levels and synapse numbers. Therefore, we demonstrated that modafinil increased cognition function and synaptic plasticity, at least in part by increasing MMP-9 expression in REM-SD rats.
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Neurons of the ventrolateral preoptic nucleus (VLPO) promote sleep and VLPO loss produces insomnia. Previous studies show that general anesthetics including isoflurane activate VLPO neurons, and may contribute to their sedative effects. However, it is not clear to what extent the activation of VLPO neurons contributes to general anesthesia. ⋯ VLPO neuron cell loss was quantified by post hoc histology. Loss of VLPO neurons as well as lesion size were associated with cumulative sleep loss (r=0.77 and r=0.62, respectively), and cumulative sleep loss was the strongest predictor of high sensitivity to anesthesia, expressed as decreased time to loss of righting reflex (-0.59), increased burst-suppression ratio (r=0.52) , and increased emergence time (r=0.54); an interaction-effect of isoflurane dose was observed (burst-suppression ratio: p<0.001). We conclude that the sleep loss caused by ablation of VLPO neurons sensitizes animals to the general anesthetic effects of isoflurane, but that the sedation produced by VLPO neurons themselves is not required for isoflurane anesthesia.
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Intracerebroventricular (ICV) streptozotocin (STZ) treated rat has been described as a suitable model for sporadic Alzheimer's disease (AD). Central application of STZ has demonstrated behavioral and neurochemical features that resembled those found in human AD. Chronic treatments with antioxidants, acetylcholinesterase (AChE) inhibitors, or improving glucose utilization drugs have reported a beneficial effect in ICV STZ-treated rats. ⋯ Memantine produced no changes in p-GSK3β levels in neither the hippocampus nor PFC. Total GSK3β levels did not change with either drug. Altogether these results show the beneficial effects of drugs with different mechanisms of actions on memory impairment induced by ICV STZ, and restored p-GSK3β levels, a kinase key of signaling cascade of insulin receptor.
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Comparative Study
Increases of antioxidants are related to more delayed neuronal death in the hippocampal CA1 region of the young gerbil induced by transient cerebral ischemia.
In age-related studies, young animals are resistant to ischemic damage. In present study, we investigated the neuronal death of pyramidal neurons and compared changes in the immunoreactivities and levels of antioxidants, Cu/Zn-SOD (SOD1), Mn-SOD (SOD2), catalase (CAT) and glutathione peroxidase (Gpx), in the hippocampal CA1 region between adult and young gerbils after 5 min of transient cerebral ischemia. In the adult ischemia-group, only a few (12%) of CA1 pyramidal neurons survived 4 days after ischemia-reperfusion (I-R); however, in the 4 days after I-R the young group, most of CA1 pyramidal neurons survived. ⋯ Four days after I-R in the adult groups, the levels of all the antioxidants were dramatically deceased; however, at this time in the young ischemia-groups, they were distinctively increased in the CA1 region. Seven days after I-R, all the antioxidants levels in the CA1 region were distinctively decreased. In brief, we conclude that the increased antioxidants levels were related to a less and much delayed neuronal death in the CA1 pyramidal neurons in the young group following I-R injury.
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The presence of a proinflammatory environment in the sensory neuron axis in diabetes was tested by measuring levels of proinflammatory cytokines in lumbar dorsal root ganglia (DRG) and peripheral nerve from age matched control and streptozotocin (STZ)-induced diabetic rats. The levels of tumor necrosis factor-α (TNFα) and other cytokines were diminished in lumbar DRG from diabetic animals. Consequently, we tested the hypothesis that TNFα modulated axonal plasticity in adult sensory neurons and posited that impairments in this signal transduction pathway may underlie degeneration in diabetic sensory neuropathy. ⋯ Immunofluorescent staining for NF-κB subunit p50 within neuronal nuclei revealed that medium to large diameter neurons were most susceptible to NF-κB inhibition and was associated with decreased neurite outgrowth. The results demonstrating reduced cytokine expression in DRG confirm that diabetic sensory neuropathy does not involve a neuroinflammatory component at this stage of the disease in experimental animal models. In addition, it is hypothesized that reduced TNFα expression in the DRG and possibly associated deficits in anterograde transport may contribute to impaired collatoral sprouting and regeneration in target tissue in type 1 diabetes.