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        Changes in the Neuronal Architecture of the Hippocampus in a 6-Hydroxydopamine-Lesioned Rat Model of Parkinson Disease

        김보혜,Poornima D. E. Weerasinghe-Mudiyanselage,Mary Jasmin Ang,이정민,강소희,김종춘,김성호,김중선,정채용,신태균,문창종 대한배뇨장애요실금학회 2022 International Neurourology Journal Vol.26 No.S2

        Purpose: Parkinson disease (PD) is a progressive neurodegenerative disorder in which dopaminergic (DAergic) systems are destroyed (particularly in the nigrostriatal system), causing both motor and nonmotor symptoms. Hippocampal neuroplasticity is altered in PD animal models, resulting in nonmotor dysfunctions. However, little is known about the precise mechanism underlying the hippocampal dysfunctions in PD. Methods: Striatal 6-hydroxydopamine (6-OHDA) infusions were performed unilaterally in adult Sprague Dawley rats. Both motor and nonmotor symptoms alongside the expression of tyrosine hydroxylase (TH) in the substantia nigra and striatum were confirmed in 6-OHDA-lesioned rats. The neuronal architecture in the hippocampus was analyzed by Golgi staining. Results: During the 7–8 weeks after infusion, the 6-OHDA-lesioned rats exhibited motor and nonmotor dysfunctions (especially anxiety/depression-like behaviors). Rats with unilateral 6-OHDA infusion displayed reduced TH+ immunoreactivity in the ipsilateral nigrostriatal pathway of the brain. Golgi staining revealed that striatal 6-OHDA infusion significantly decreased the dendritic complexity (i.e., number of crossing dendrites, total dendritic length, and branch points) in the ipsilateral hippocampal conus ammonis 1 (CA1) apical/basal and dentate gyrus (DG) subregions. Additionally, the dendritic spine density and morphology were significantly altered in the CA1 apical/basal and DG subregions following striatal 6-OHDA infusion. However, alteration of microglial and astrocytic distributions did not occur in the hippocampus following striatal 6-OHDA infusion. Conclusions: The present study provides anatomical evidence that the structural plasticity in the hippocampus is altered in the late phase following striatal 6-OHDA infusion in rats, possibly as a result of the prolonged suppression of the DAergic system, and independent of neuroinflammation.

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        Retinal transcriptome profiling identifies novel candidate genes associated with visual impairment in a mouse model of multiple sclerosis

        홍성무,Poornima D. E. Weerasinghe-Mudiyanselage,강소희,문창종,신태균 한국통합생물학회 2023 Animal cells and systems Vol.27 No.1

        Visual impairment is occasionally observed in multiple sclerosis (MS) and its animal model,experimental autoimmune encephalomyelitis (EAE). Although uveitis and optic neuritis havebeen reported in MS and EAE, the precise mechanisms underlying the pathogenesis of thesevisual impairments remain poorly understood. This study aims to identify differentiallyexpressed genes (DEGs) in the retinas of mice with EAE to identify genes that may beimplicated in EAE-induced visual impairment. Fourteen adult mice were injected with myelinoligodendrocyte glycoprotein35–55 to induce the EAE model. Transcriptomes of retinas with EAEwere analyzed by RNA-sequencing. Gene expression analysis revealed 347 DEGs in the retinas ofmice with EAE: 345 were upregulated, and 2 were downregulated (adjusted p-value < 0.05 andabsolute log2 fold change > 1). Gene ontology (GO) analysis showed that the upregulated genesin the retinas of mice with EAE were primarily related to immune responses, responses toexternal biotic stimuli, defense responses, and leukocyte-mediated immunity in the GObiological process. The expression of six upregulated hub genes (c1qb, ctss, itgam, itgb2, syk,and tyrobp) from the STRING analysis and the two significantly downregulated DEGs (hapln1and ndst4) were validated by reverse transcription-quantitative polymerase chain reaction. Inaddition, gene set enrichment analysis showed that the negatively enriched gene sets in EAEaffectedretinas were associated with the neuronal system and phototransduction cascade. Thisstudy provides novel molecular evidence for visual impairments in EAE and indicates directionsfor further research to elucidate the mechanisms of these visual impairments in MS.

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