Background: Cofilin rods are associated with Alzheimer disease, but their pathological significance is unclear. Results: Time-lapse imaging revealed that cofilin rods inhibit the movement of mitochondria and early endosomes. Cofilin rods reduce dendritic spines and impair synaptic transmission. Cofilin rods are discovered in senile rat brains. Conclusion: Cofilin rods block intracellular transport and induce synaptic loss. Significance: Our work identifies a signaling pathway underlying neurodegeneration and brain aging.

Circular RNAs (circRNAs), a novel kind of non-coding RNA, have received increasing attention for their involvement in pathogenesis of Alzheimer’s disease (AD); however, few studies have reported in the characterization and function of AD associated circRNAs. Here the expression profiles of circRNAs in 5- and 10-month-old SAMP8 mice were identified using circRNA microarray and found that 85 dysregulated circRNAs were observed in 10-month-old SAMP8 versus control mice and 231 circRNAs exhibited differential expression in 10-month-old SAMP8 versus 5-month-old SAMP8. One most significantly dysregulated circRNA, mmu_circRNA_017963, was select for Gene Oncology (GO) and pathway analysis. The results showed that mmu_circRNA_017963 was strongly related with autophagosome assembly, exocytosis, apoptotic process, transport and RNA splicing and highly associated with synaptic vesicle cycle, spliceosome, glycosaminoglycan and SNARE interactions in vesicular transport pathways. Collectively, this study was the first to describe circRNAs expression in different ages of SAMP8 and will contribute to the understanding of the regulatory roles of circRNAs in AD pathogenesis and provide a valuable resource for the diagnosis and therapy of AD.

Ischemic stroke not only induces neuron death in the infarct area but also structural and functional damage of the surviving neurons in the surrounding peri-infarct area. In the present study, we first identified cofilin rod, a pathological rod-like aggregation, formed in neurons of in vivo ischemic stroke animal model and induced neuronal impairment. Cofilin rods formed only on the ipsilateral side of the middle cerebral artery occlusion and reperfusion (MCAO-R) rat brain and showed the highest density in peri-infarct area. Our real-time live cell imaging, immunostaining and patch clamp studies showed that cofilin rod formation in neurons led to dendritic mitochondrial transportation failure, as well as impairment of synaptic structure and functions. Overexpression of LIM kinase or activation of its upstream regulator Rho, suppressed ischemia-induced cofilin rod formation and showed protective effect on synaptic function and structure impairment in both cultured neurons and MCAO-R rat model. In summary, our results demonstrate a novel mechanism of ischemic stroke-induced neuron injury in peri-infarct area and provide a potential target for the protection of neuronal structure and function against brain ischemia insult.

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Phenol red is widely used in cell culture as a pH indicator. Recently, it also has been reported to have estrogen-like bioactivity and be capable of promoting cell proliferation in different cell lines. However, the effect of phenol red on primary neuronal culture has never been investigated. By using patch clamp technique, we demonstrated that hippocampal pyramidal neurons cultured in neurobasal medium containing no phenol red had large depolarization-associated epileptiform bursting activities, which were rarely seen in neurons cultured in phenol red-containing medium. Further experiment data indicate that the suppressive effect of the phenol red on the abnormal epileptiform burst neuronal activities was U-shape dose related, with the most effective concentration at 28 µM. In addition, this concentration related inhibitory effect of phenol red on the epileptiform neuronal discharges was mimicked by 17-β-estradiol, an estrogen receptor agonist, and inhibited by ICI-182,780, an estrogen receptor antagonist. Our results suggest that estrogen receptor activation by phenol red in the culture medium prevents formation of abnormal, epileptiform burst activity. These studies highlight the importance of phenol red as estrogen receptor stimulator and cautions of careful use of phenol red in cell culture media.

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Toxic inhibition and wash-out of nitrifying bacteria in traditional single-activated sludge processes frequently cause instability of nitrification in industrial wastewater treatment and limit the total nitrogen (TN) removal efficiency. A novel oxic–hydrolytic–oxic (O/H/O) process based on a three-sludge regime was developed to treat coking wastewater with a high C/N ratio and biological toxicity. The results demonstrated that high COD removal (89.6%, 91.3%, 90.4%, and 87.1% in four different modes) was achieved with the complete elimination of phenol, sulfide, total cyanide, and thiocyanate. TN removal varied from 14.0% to 88.7% at an influent flow of 1.6–2.0 kg of COD m–3 day–1, depending on prenitrification, internal recycling, and the presence of a sufficient carbon source for denitrification. The first oxic (O1) and hydrolytic (H) reactors made predominant contributions to the removal of organic and toxic pollutants. The removal of these pollutants guaranteed a stable and favorable environment for nitrification in the second oxic (O2) reactor, in which high ammonium removal was observed because of the predominance of Nitrosomonas and Nitrospira. The O/H/O process has the potential to become a promising industrial wastewater treatment process because it promotes functions that are independent of microbial and process stability with respect to the removal of pollutants, especially nitrogen.