Rattus norvegicus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA124409 | ENA |
REPOSITORIES: ENA
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Project description:Injury of descending motor tracts remodels cortical circuitry and leads to enhanced neuronal excitability, thus influencing recovery following injury. The neuron-specific contributions remain unclear due to the complex cellular composition and connectivity of the CNS. We developed a microfluidics-based in vitro model system to examine intrinsic synaptic remodeling following axon damage. We found that distal axotomy of cultured rat pyramidal neurons caused dendritic spine loss at synapses onto the injured neurons followed by a persistent retrograde enhancement in presynaptic excitability over days. These in vitro results mirrored hyper-activity of directly injured corticospinal neurons in hindlimb motor cortex layer Vb following spinal cord contusion. In vitro axotomy-induced hyper-excitability coincided with elimination of inhibitory presynaptic terminals, including those formed onto dendritic spines. We identified netrin-1 as downregulated following axotomy and exogenous netrin-1 applied 2 days after injury normalized spine density, presynaptic excitability, and the fraction of inhibitory inputs onto injured neurons. These findings demonstrate a novel model system for studying the response of pyramidal circuitry to axotomy and provide new insights of neuron-specific mechanisms that contribute to synaptic remodeling.
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Project description:Inflammation is a key component of pathological angiogenesis. Here we induce cornea neovascularisation using sutures placed into the cornea, and sutures are removed to induce a regression phase. We used whole transcriptome microarray to monitor gene expression profies of several genes
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Project description:Knee osteoarthritis (KOA), as a degenerative multifactorial disease, affects the quality of life and mental health of patients, and also brings a huge socioeconomic burden. Treating synovitis have shown promise as anti-inflammatory therapeutics in mitigating OA symptoms and disease progression. Here, by analysing synovial single-cell sequencing (scRNA-seq) data from KOA, we found that synovial fibroblasts (FLS) in OA synovium showed a distinct pro-inflammatory phenotype. We collected synovial tissue from patients with clinical OA as well as from healthy donors, and histological examination was consistent with findings in scRNA-seq. Inspired by recent cross-tissue fibroblast lineage studies, we identified by sequencing that healthy FLS in synovial tissues share transcriptome-level similarities with dermal fibroblasts (DFb). Subsequently, we revealed the local as well as systemic distribution of intra-articular injected DFbs by constructing/extracting two types of rat fibroblasts (luciferase DFbs as well as GFP DFbs). The results demonstrate that DFbs can be locally retained in the synovium for up to three weeks following targeted engrafting on it. And intra-articular injection does not result in DFbs migration to vital organs or the occurrence of histological changes in these organs. A rat model of KOA was constructed by anterior cruciate ligament transection (ACLT) in order to study the therapeutic effect of DFbs on KOA. After injection, the rats showed improvement in painful gait. In addition, histological as well as imaging results showed reduced synovitis and improvement in articular cartilage. Finally we verified the protective effect of DFbs on cytokine-stimulated chondrocytes in a co-culture system.
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