Neuroscience
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Ammonia inhibits long-term potentiation via neurosteroid synthesis in hippocampal pyramidal neurons.
Neurosteroids are a class of endogenous steroids synthesized in the brain that are believed to be involved in the pathogenesis of neuropsychiatric disorders and memory impairment. Ammonia impairs long-term potentiation (LTP), a synaptic model of learning, in the hippocampus, a brain region involved in memory acquisition. Although mechanisms underlying ammonia-mediated LTP inhibition are not fully understood, we previously found that the activation of N-methyl-d-aspartate receptors (NMDARs) is important. ⋯ Finasteride also overcame LTP inhibition by 100 μM ammonia, as did picrotoxin, an inhibitor of GABA-A receptors. These results indicate that GABA-enhancing neurosteroids, synthesized locally within pyramidal neurons, contribute significantly to ammonia-mediated synaptic dysfunction. These results suggest that the manipulation of neurosteroid synthesis could provide a strategy to improve cognitive function in individuals with hyperammonemia.
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Comparative Study
Comparing the after-effects of continuous theta burst stimulation and conventional 1 Hz rTMS on semantic processing.
Our aim was to evaluate continuous theta burst stimulation (cTBS) as a tool to induce temporary impairment (virtual lesion) in semantic processing. Four groups with 20 subjects each were stimulated. In the three experimental groups the stimulation site was the left superior temporal cortex. ⋯ The effect lasted for the whole task, but declined from the first to the second half of the experiment. The direct comparison of cTBS and 1 Hz rTMS suggests that both stimulation patterns can induce virtual lesions in the left superior temporal cortex and impair semantic processing. We suppose that cTBS could replace 1 Hz rTMS in this field since the application is faster and it is more comfortable to the subjects.
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Previous studies have shown that running exercise could increase regional cerebral blood flow. There have been previous studies investigating the effects of running exercise on capillary density in the brain and showing that running exercise could induce brain angiogenesis. However, there have been no studies investigating the effects of running exercise on the total volume, total length and total surface area of the capillaries in the cortex. ⋯ Our results also reveal that there are sex differences in the effects of running exercise on the capillaries in the cortex of middle-aged rats. These results demonstrate that exercise-induced increases of the capillaries in the female rat cortex might be one of the structural bases for the exercise-induced improvement in the spatial learning capacity of middle-aged female rats. These results provide a baseline for further studies that search for strategies to delay the deleterious effects of brain aging.
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Parkinson's disease (PD) is an asymmetric neurodegenerative disorder, and secondary adaptive mechanisms of the less-affected side could potentially compensate for parkinsonian symptoms. Here, we analyzed gene expression changes on the healthy side of a unilateral PD rat model and correlated these changes with locomotor velocity, which is known to be decreased in PD. Four weeks after a unilateral 6-hydroxydopamine lesion, the spontaneous locomotor velocity of rats was recorded just prior to brain extraction. ⋯ In contrast, no contralateral changes were observed in the striatal indirect pathway. We also did not find any significant contralateral modifications of TH, DAT or glutamatergic markers in PD animals, indicating that changes in direct pathway genes are not due to nigrostriatal dopaminergic or corticostriatal glutamatergic innervation. In conclusion, our results suggest a role of the healthy striatal direct pathway in counteracting dopaminergic denervation effects on motor symptoms.
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Heroin is reported to cause spongiform leukoencephalopathy (SLE) in heroin addicts and the exact mechanism has not yet been identified. In the present study, we found that heroin could induce apoptosis of primary cultured cerebellar granule cells (CGCs) and Bim was upregulated both transcriptionally and post transcriptionally during CGCs apoptosis. Upregulated Bim translocated to mitochondria and Bax was activated under heroin treatment. ⋯ Bim was demonstrated as a downstream target of JNK/c-Jun pathway in this process because pharmacological inhibition of JNK reduced the levels of Bim mRNA and protein. These results indicate that Bim plays a critical role in the neurotoxic process by heroin and JNK/c-Jun pathway acts upstream of Bim in regulating heroin-induced neuronal death. This represents a detailed mechanism of heroin-induced neuronal apoptosis and may provide a new and effective strategy to treat heroin-induced addiction and SLE.