- 标题
- 摘要
- 关键词
- 实验方案
- 产品
-
Retinal Neuroprotection From Optic Nerve Trauma by Deletion of Arginase 2
摘要： Our previous studies have implicated expression of the mitochondrial isoform of the arginase enzyme arginase 2 (A2) in neurovascular injury during ischemic retinopathies. The aim of this study was to characterize the specific involvement of A2 in retinal injury following optic nerve crush (ONC). To accomplish this, wild-type (WT) or A2 knockout (A2?/?) mice were subjected to ONC injury. The contralateral eye served as sham control. Quantitative RT-PCR and western blot were used to evaluate mRNA and protein expression. Retinal ganglion cell (RGC) survival was assessed in retinal whole mounts. Axonal sprouting was determined by anterograde transport of Cholera Toxin B (CTB). These analyses showed increased A2 expression following ONC. Numbers of NeuN-positive neurons as well as Brn3a- and RBPMS-positive RGC were decreased in the WT retinas at 14 days after ONC as compared to the sham controls. This ONC-induced neuronal loss was diminished in the A2?/? retinas. Similarly, axonal degeneration was ameliorated by A2 deletion whereas axon sprouting was enhanced. Significant retinal thinning was also seen in WT retinas at 21 days after ONC, and this was blocked in A2?/? mice. Cell death studies showed an increase in TUNEL positive cells in the RGC layer at 5 days after ONC in the WT retinas, and this was attenuated by A2 deletion. ONC increased glial cell activation in WT retinas, and this was significantly reduced by A2 deletion. Western blotting showed a marked increase in the neurotrophin, brain derived neurotrophic factor (BDNF) and its downstream signaling in A2?/? retinas vs. WT after ONC. This was associated with increases in the axonal regeneration marker GAP-43 in A2?/? retinas. Furthermore, A2?/? retinas showed decreased NLRP3 inflammasome activation and lower interleukin (IL-) 1β/IL-18 levels as compared to WT retinas subjected to ONC. Collectively, our results show that deletion of A2 limits ONC-induced neurodegeneration and glial activation, and enhances axonal sprouting by a mechanism involving increases in BDNF and decreases in retinal inflammation. These data demonstrate that A2 plays an important role in ONC-induced retinal damage. Blockade of A2 activity may offer a therapeutic strategy for preventing vision loss induced by traumatic retinal injury.
关键词： optic nerve crush,retinal ganglion cells,retina,brain derived neurotrophic factor,neuroprotection,arginase 2
更新于2025-09-23 15:23:52
-
MicroRNA-382 inhibits cell proliferation and invasion of retinoblastoma by targeting BDNF-mediated PI3K/AKT signalling pathway
摘要： It has previously been demonstrated that multiple microRNAs (miRNAs or miRs) are aberrantly expressed in retinoblastoma (RB) and contribute to RB initiation and progression. miR-382 has been revealed to be aberrantly expressed and therefore exhibits a key role in the progression of various types of cancer. However, the expression pattern, functional roles and underlying molecular mechanism of miR-382 in RB remain unknown. The present study investigated the expression levels of miR-382 and its effects on RB cells and the underlying regulatory mechanism of its action. It was demonstrated that miR-382 was downregulated in RB tissues and cell lines. Upregulation of miR-382 inhibited RB cell proliferation and invasion in vitro. Additionally, brain-derived neurotrophic factor (BDNF) was identified as a novel target of miR-382 in RB. BDNF was upregulated in RB tissues and negatively associated with miR-382 expression levels. Furthermore, BDNF overexpression rescued the tumour-suppressing effects on RB cells induced by miR-382. miR-382 inactivated the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signalling pathway in RB. These findings suggested that miR-382 serves as a tumour suppressor in RB, in part, by targeting the BDNF-mediated PI3K/AKT signalling pathway. The results of the present study suggest a potential therapeutic strategy for treating RB patients in the future.
关键词： PI3K/AKT,microRNA-382,brain-derived neurotrophic factor,retinoblastoma
更新于2025-09-23 15:22:29
-
High performance nBn detectors based on InGaAsSb bulk materials for short wavelength infrared detection
摘要： Objective: To investigate whether hydrogen sulfide (H2S) counteracts formaldehyde (FA)-induced cognitive defects and whether the underlying mechanism is involved in the upregulation of hippocampal brain-derived neurotrophic factor (BDNF) expression. Methods: The cognitive function of rats was evaluated by the Morris water maze (MWM) test and the novel object recognition test. The content of superoxide dismutase (SOD) and malondialdehyde (MDA) in the hippocampus were detected by enzyme-linked immunosorbent assay (ELISA). The neuronal apoptosis in the hippocampal CA1 region was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end (TUNEL) staining. The expression of the BDNF protein was detected by Western blot and immunohistochemistry. Results: We found that sodium hydrosulfide (NaHS, a donor of H2S) significantly reversed the impairment in the function of learning and memory in the MWM test and the novel objective recognition task induced by intracerebroventricular injection of FA. We also showed that NaHS significantly reduced the level of MDA, elevated the level of SOD, and decreased the amount of TUNEL-positive neurons in the hippocampus of FA-exposed rats. Moreover, NaHS markedly increased the expression of hippocampal BDNF in FA-exposed rats. Conclusions: H2S attenuates FA-induced dysfunction of cognition and the underlying mechanism is involved in the reduction of hippocampal oxidative damage and apoptosis as well as upregulation of hippocampal BDNF.
关键词： Cognitive defect,Oxidative stress,Brain-derived neurotrophic factor,Formaldehyde,Hydrogen sulfide,Apoptosis
更新于2025-09-19 17:13:59