MicroRNAs: protective regulators for neuron growth and development.

MicroRNAs (miRNAs) play an important regulatory role in neuronal growth and development. Different miRNAs target different genes to protect neurons in different ways, such as by avoiding apoptosis, preventing degeneration mediated by conditional mediators, preventing neuronal loss, weakening certain neurotoxic mechanisms, avoiding damage to neurons, and reducing inflammatory damage to them. The high expression of miRNAs in the brain has significantly facilitated their development as protective targets for therapy, including neuroprotection and neuronal recovery. miRNA is indispensable to the growth and development of neurons, and in turn, is beneficial for the development of the brain and checking the progression of various diseases of the nervous system. It can thus be used as an important therapeutic target for models of various diseases. This review provides an introduction to the protective effects of miRNA on neurons in case of different diseases or damage models, and then provides reference values and reflections on the relevant treatments for the benefit of future research in the area.

Cortical regulation of striatal projection neurons and interneurons in a Parkinson's disease rat model.

Striatal neurons can be either projection neurons or interneurons, with each type exhibiting distinct susceptibility to various types of brain damage. In this study, 6-hydroxydopamine was injected into the right medial forebrain bundle to induce dopamine depletion, and/or ibotenic acid was injected into the M1 cortex to induce motor cortex lesions. Immunohistochemistry and western blot assay showed that dopaminergic depletion results in significant loss of striatal projection neurons marked by dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein, molecular weight 32 kDa, calbindin, and µ-opioid receptor, while cortical lesions reversed these pathological changes. After dopaminergic deletion, the number of neuropeptide Y-positive striatal interneurons markedly increased, which was also inhibited by cortical lesioning. No noticeable change in the number of parvalbumin-positive interneurons was found in 6-hydroxydopamine-treated rats. Striatal projection neurons and interneurons show different susceptibility to dopaminergic depletion. Further, cortical lesions inhibit striatal dysfunction and damage induced by 6-hydroxydopamine, which provides a new possibility for clinical treatment of Parkinson's disease.

Microglia activation: one of the checkpoints in the CNS inflammation caused by Angiostrongylus cantonensis infection in rodent model.

Angiostrongylus cantonensis (A. cantonensis) is a rodent nematode. Adult worms of A. cantonensis live in the pulmonary arteries of rats; humans are non-permissive hosts like the mice. The larva cannot develop into an adult worm and only causes serious eosinophilic meningitis or meningo-encephalitis if humans or mice eat food containing larva of A. cantonensis in the third stage. The differing consequences largely depend on differing immune responses of hosts to parasite during A. cantonensis invasion and development. To further understand the reasons why mice and rats attain different outcomes in A. cantonensis infection, we used the HE staining to observe the pathological changes of infected mice and rats. In addition, we measured mRNA levels of some cytokines (IL-5, IL-6, IL-13, Eotaxin, IL-4, IL-10, TGF-ß, IFN-γ, IL-17A, TNF-α, IL-1ß, and iNOS) in brain tissues of mice and rats by real-time PCR. The result showed that brain inflammation in mice was more serious than in rats. Meanwhile, mRNA expression levels of IL-6, IL-1ß, TNF-α, and iNOS increased after mice were infected. In contrast, mRNA levels of these cytokines in rats brain tissues decreased at post- infection 21 days. These cytokines mostly were secreted by activated microglia in central nervous system. Microglia of mice and rats were showed by Iba-1 (microglia marker) staining. In micee brains, microglia got together and had more significant activation than in rats brains. The results demonstrate that mice and rats have different CNS inflammation after infection by A. cantonensis, and it is in line with other researchers' reported findings. In conclusion, it is suggested that microglia activation is probably to be one of the most important factors in angiostrongyliasis from our study.

EPO-dependent activation of PI3K/Akt/FoxO3a signalling mediates neuroprotection in in vitro and in vivo models of Parkinson's disease.

Erythropoietin (EPO) may become a potential therapeutic candidate for the treatment of the neurodegenerative disorder -- Parkinson's disease (PD), since EPO has been found to prevent neuron apoptosis through the activation of cell survival signalling. However, the underlying mechanisms of how EPO exerts its neuroprotective effect are not fully elucidated. Here we investigated the mechanism by which EPO suppressed 6-hydroxydopamine (6-OHDA)-induced neuron death in in vitro and in vivo models of PD. EPO knockdown conferred 6-OHDA-induced cytotoxicity. This effect was reversed by EPO administration. Treatment of PC12 cells with EPO greatly diminished the toxicity induced by 6-OHDA in a dose- and time-dependent manner. EPO effectively reduced apoptosis of striatal neurons and induced a significant improvement on the neurological function score in the rat models of PD. Furthermore, EPO increased the expression of phosphorylated Akt and phosphorylated FoxO3a, and abrogated the 6-OHDA-induced dysregulation of Bcl-2, Bax and Caspase-3 in PC12 cells and in striatal neurons. Meanwhile, the EPO-dependent neuroprotection was notably reversed by pretreatment with LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K). Our data suggest that PI3K/Akt/FoxO3a signalling pathway may be a possible mechanism involved in the neuroprotective effect of EPO in PD.

Establishment of rat model for Pneumocystis carinii infection and cloning of the surface glycoprotein A gene of Pneumocystis carinii.

OBJECTIVE: To establish a rat model for Pneumocystis carinii infection and to clone surface glycoprotein A (GpA) gene of Pneumocystis carini. METHODS: Immunosuppression was induced in 5 rats with an immunosuppresion regimen consisting mainly of dexamethasone in a course of 2 weeks, after which pulmonary homogenates of rats infected with Pneumocystis carinii were fed to the immunosuppressed rats. Immunosuppression was maintained for approximately 4 weeks after the feeding to induce Pneumocystis pneumonia in the rats. GpA gene was subsequently amplified from the rats with pneumonia as confirmed by microscope and PCR detection, and was subcloned into T-vector for the transformation of Escherichia coli JM109 strain. RESULTS: Pneumocystis carinii was detected by microscope and PCR detection in rats with immunosuppression. The length of PCR product was 319 bp as shown by agarose electrophoresis. CONCLUSION: The rat model of Pneumocystis carinii infection can be established by immunosuppression with dexamethasone and a single oral administration of the pathogen.