Dataset Information

Voluntary running delays primary degeneration in rat retinas after partial optic nerve transection.

ABSTRACT: Running is believed to be beneficial for human health. Many studies have focused on the neuroprotective effects of voluntary running on animal models. There were both primary and secondary degeneration in neurodegenerative diseases, including glaucoma. However, whether running can delay primary or secondary degeneration or both of them was not clear. Partial optic nerve transection model is a valuable glaucoma model for studying both primary and secondary degeneration because it can separate primary (mainly in the superior retina) from secondary (mainly in the inferior retina) degeneration. Therefore, we compared the survival of retinal ganglion cells between Sprague-Dawley rat runners and non-runners both in the superior and inferior retinas. Excitotoxicity, oxidative stress, and apoptosis are involved in the degeneration of retinal ganglion cells in glaucoma. So we also used western immunoblotting to compare the expression of some proteins involved in apoptosis (phospho-c-Jun N-terminal kinases, p-JNKs), oxidative stress (manganese superoxide dismutase, MnSOD) and excitotoxicity (glutamine synthetase) between runners and non-runners after partial optic nerve transection. Results showed that voluntary running delayed the death of retinal ganglion cells vulnerable to primary degeneration but not those to secondary degeneration. In addition, voluntary running decreased the expression of glutamine synthetase, but not the expression of p-JNKs and MnSOD in the superior retina after partial optic nerve transection. These results illustrated that primary degeneration of retinal ganglion cells might be mainly related with excitotoxicity rather than oxidative stress; and the voluntary running could down-regulate excitotoxicity to delay the primary degeneration of retinal ganglion cells after partial optic nerve transection.

SUBMITTER: Li HY

PROVIDER: S-EPMC6352605 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Voluntary running delays primary degeneration in rat retinas after partial optic nerve transection.

Li Hong-Ying HY Hong Xi X Huang Mi M So Kwok-Fai KF

Neural regeneration research 20190401 4

Running is believed to be beneficial for human health. Many studies have focused on the neuroprotective effects of voluntary running on animal models. There were both primary and secondary degeneration in neurodegenerative diseases, including glaucoma. However, whether running can delay primary or secondary degeneration or both of them was not clear. Partial optic nerve transection model is a valuable glaucoma model for studying both primary and secondary degeneration because it can separate pri ...[more]

PMID: 30632515

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Project description:PurposeA time-course analysis of gene regulation in the adult rat retina after intraorbital nerve crush (IONC) and intraorbital nerve transection (IONT).MethodsRNA was extracted from adult rat retinas undergoing either IONT or IONC at increasing times post-lesion. Affymetrix RAE230.2 arrays were hybridized and analyzed. Statistically regulated genes were annotated and functionally clustered. Arrays were validated by means of quantative reverse transcription polymerase chain reaction (qRT-PCR) on ten regulated genes at two times post-lesion. Western blotting and immunohistofluorescence for four pro-apoptotic proteins were performed on naïve and injured retinas. Finally, custom signaling maps for IONT- and IONC-induced death response were generated (MetaCore, Genego Inc.).ResultsHere we show that over time, 3,219 sequences were regulated after IONT and 1,996 after IONC. Out of the total of regulated sequences, 1,078 were commonly regulated by both injuries. Interestingly, while IONT mainly triggers a gene upregulation-sustained over time, IONC causes a transitory downregulation. Functional clustering identified the regulation of high interest biologic processes, most importantly cell death wherein apoptosis was the most significant cluster. Ten death-related genes upregulated by both injuries were used for array validation by means of qRT-PCR. In addition, western blotting and immunohistofluorescence of total and active Caspase 3 (Casp3), tumor necrosis factor receptor type 1 associated death domain (TRADD), tumor necrosis factor receptor superfamily member 1a (TNFR1a), and c-fos were performed to confirm their protein regulation and expression pattern in naïve and injured retinas. These analyses demonstrated that for these genes, protein regulation followed transcriptional regulation and that these pro-apoptotic proteins were expressed by retinal ganglion cells (RGCs). MetaCore-based death-signaling maps show that several apoptotic cascades were regulated in the retina following optic nerve injury and highlight the similarities and differences between IONT and IONC in cell death profiling.ConclusionsThis comprehensive time course retinal transcriptome study comparing IONT and IONC lesions provides a unique valuable tool to understand the molecular mechanisms underlying optic nerve injury and to design neuroprotective protocols.

Project description:Background:Reactive oxygen species (ROS) induced oxidative stress is linked to numerous neurological diseases, including neuropathic pain. Natural ROS scavenging enzymes like superoxide dismutase (SOD) and catalase have been found to be efficient in alleviating neuropathic pain. However, their sensitivity towards extreme pH and a short half-life limit their efficacy in vivo. Manganese oxide nanoparticles (MONPs) are recently known to possess ROS scavenging properties. In this study, MONPs were examined for their therapeutic effect on neuropathic pain. Methods:The MONPs were synthesized by a hydrothermal method. The synthesized MONPs were characterized by UV/Vis, TEM, SEM, FTIR, NTA and XRD. The biocompatibility of the nanoparticles is evaluated in neural cells using LDH assay. MONPs were evaluated for their antioxidant activity by DPPH assay. In addition, in vitro ROS scavenging properties were examined in bone marrow-derived macrophage (BMDM) cells using 2',7'-dichlorofluorescin diacetate (DCFDA) assay. To evaluate the in vivo efficacy of nanoparticles, neuropathic pain was induced in Wistar rats by partial sciatic nerve transection (PSNT). On post-transection days 14 to 18, rats were intrathecally injected with MONPs and paw withdrawal threshold was measured. The spinal cords were collected and processed for Western blotting and histological analysis. Results:The synthesized MONPs were biocompatible and showed effective antioxidant activity against DPPH free radical scavenging. Further, the nanoparticles scavenged ROS efficiently in vitro in BMDM and their intrathecal administration significantly reduced mechanical allodynia as well as the expression of cyclooxygenase-2 (COX-2), an important mediator of chronic and inflammatory pain in the spinal dorsal horns of PSNT rats. Conclusion:As ROS play a significant role in neuropathic pain, we expect that MONPs could be a promising tool for the treatment of various inflammatory diseases and might also serve as a potential nanocarrier for the delivery of analgesics.

Dataset Information

Voluntary running delays primary degeneration in rat retinas after partial optic nerve transection.

Publications

Voluntary running delays primary degeneration in rat retinas after partial optic nerve transection.

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