Search results for "57"
showing 10 items of 4186 documents
Rhythmic Regulation of Photoreceptor and RPE Genes Important for Vision and Genetically Associated With Severe Retinal Diseases.
2018
Purpose The aim of the present study was to identify candidate genes for mediating daily adjustment of vision. Methods Genes important for vision and genetically associated with severe retinal diseases were tested for 24-hour rhythms in transcript levels in neuronal retina, microdissected photoreceptors, photoreceptor-related pinealocytes, and retinal pigment epithelium-choroid (RPE-choroid) complex by using quantitative PCR. Results Photoreceptors of wildtype mice display circadian clock-dependent regulation of visual arrestins (Arr1, Arr4) and the visual cycle gene Rdh12, whereas cells of the RPE-choroid exhibit light-dependent regulation of the visual cycle key genes Lrat, Rpe65, and Rdh…
Synergistic action of CB1 and 5-HT2B receptors in preventing pilocarpine-induced status epilepticus in rats
2019
Abstract Endocannabinoids (eCBs) and serotonin (5-HT) play a neuromodulatory role in the central nervous system. Both eCBs and 5-HT regulate neuronal excitability and their pharmacological potentiation has been shown to control seizures in pre-clinical and human studies. Compelling evidence indicates that eCB and 5-HT systems interact to modulate several physiological and pathological brain functions, such as food intake, pain, drug addiction, depression, and anxiety. Nevertheless, there is no evidence of an eCB/5-HT interaction in experimental and human epilepsies, including status epilepticus (SE). Here, we performed video-EEG recording in behaving rats treated with the pro-convulsant age…
The role of myoglobin in epithelial cancers: Insights from transcriptomics
2019
The muscle-associated respiratory protein myoglobin (MB) is expressed in multiple types of cancer, including breast and prostate tumors. In Kaplan-Meier analyses of the two tumor types, MB positivity is associated with favorable prognoses. Despite its well-characterized function in myocytes, the role of MB in cancer remains unclear. To study the impact of endogenous MB expression, small interfering RNA MB-knockdown cells were engineered using breast, prostate and colon cancer cell lines (MDA-MB468, LNCaP, DLD-1), and their transcriptomes were investigated using RNA-Seq at different oxygen levels. In MB-positive cells, increased expression of glycolytic genes was observed, which was possibly…
12q14.3 microdeletion involving HMGA2 gene cause a Silver-Russell syndrome-like phenotype: a case report and review of the literature
2020
Abstract Background Silver-Russell Syndrome (SRS) is a genetic disorder characterized by intrauterine and postnatal growth restriction and normal head circumference with consequent relative macrocephaly. Addictional findings are protruding forehead in early life, body asymmetry (of upper and lower limbs) and substantial feeding difficulties. Although several genetic mechanisms that cause the syndrome are known, more than 40% of patients with a SRS-like phenotype remain without an etiological diagnosis. In the last few years, different clinical reports have suggested that mutations or deletions of the HMGA2 gene can be responsible for a SRS-like phenotype in patients with negative results of…
General control non-derepressible 2 (GCN2) in T cells controls disease progression of autoimmune neuroinflammation.
2016
Relapsing-remitting multiple sclerosis (MS)(2) is characterized by phases of acute neuroinflammation followed by spontaneous remission. Termination of inflammation is accompanied by an influx of regulatory T cells (Tregs).(3) The molecular mechanisms responsible for directing Tregs into the inflamed CNS tissue, however, are incompletely understood. In an MS mouse model we show that the stress kinase general control non-derepressible 2 (GCN2),(4) expressed in T cells, contributes to the resolution of autoimmune neuroinflammation. Failure to recover from acute inflammation was associated with reduced frequencies of CNS-infiltrating Tregs. GCN2 deficient Tregs displayed impaired migration to a…
Bioenergetic shift and actin cytoskeleton remodelling as acute vascular adaptive mechanisms to angiotensin II in murine retina and ophthalmic artery
2020
Ocular vascular dysfunction is a major contributing factor to the pathogenesis of glaucoma. In recent years, there has been a renewed interest in the role of angiotensin II (Ang II) in mediating the disease progression. Despite its (patho)physiological importance, the molecular mechanisms underlying Ang II-mediated oxidative stress remain largely unexplored in the ocular vasculature. Here, we provide the first direct evidence of the alterations of proteome and signalling pathways underlying Ang II-elicited oxidative insult independent of arterial pressure changes in the ophthalmic artery (OA) and retina (R) employing an in vitro experimental model. Both R and OA were isolated from male C57B…
Activation of Corticothalamic Layer 6 Cells Decreases Angular Tuning in Mouse Barrel Cortex.
2019
In the mouse whisker system, the contribution of L6 corticothalamic cells (L6 CT) to cortical and thalamic processing of the whisker deflection direction was investigated. A genetically defined population of L6 CT cells project to infragranular GABAergic interneurons that hyperpolarize neurons in somatosensory barrel cortex (BC). Optogenetic activation of these neurons switched BC to an adapted mode in which excitatory cells lost their angular tuning. In contrast, however, this was not the case with a general activation of inhibitory interneurons via optogenetic activation of Gad2-expressing cells. The decrease in angular tuning, when L6 CT cells were activated, was due to changes in cortic…
Functional hypoxia drives neuroplasticity and neurogenesis via brain erythropoietin.
2020
Erythropoietin (EPO), named after its role in hematopoiesis, is also expressed in mammalian brain. In clinical settings, recombinant EPO treatment has revealed a remarkable improvement of cognition, but underlying mechanisms have remained obscure. Here, we show with a novel line of reporter mice that cognitive challenge induces local/endogenous hypoxia in hippocampal pyramidal neurons, hence enhancing expression of EPO and EPO receptor (EPOR). High-dose EPO administration, amplifying auto/paracrine EPO/EPOR signaling, prompts the emergence of new CA1 neurons and enhanced dendritic spine densities. Single-cell sequencing reveals rapid increase in newly differentiating neurons. Importantly, i…
Blimp1 Prevents Methylation of Foxp3 and Loss of Regulatory T Cell Identity at Sites of Inflammation
2018
Summary Foxp3+ regulatory T (Treg) cells restrict immune pathology in inflamed tissues; however, an inflammatory environment presents a threat to Treg cell identity and function. Here, we establish a transcriptional signature of central nervous system (CNS) Treg cells that accumulate during experimental autoimmune encephalitis (EAE) and identify a pathway that maintains Treg cell function and identity during severe inflammation. This pathway is dependent on the transcriptional regulator Blimp1, which prevents downregulation of Foxp3 expression and “toxic” gain-of-function of Treg cells in the inflamed CNS. Blimp1 negatively regulates IL-6- and STAT3-dependent Dnmt3a expression and function …
Temporal profiling of an acute stress-induced behavioral phenotype in mice and role of hippocampal DRR1.
2018
Abstract Understanding the neurobiological mechanisms underlying the response to an acute stressor may provide novel insights into successful stress-coping strategies. Acute behavioral stress-effects may be restricted to a specific time window early after stress-induction. However, existing behavioral test batteries typically span multiple days or even weeks, limiting the feasibility for a broad behavioral analysis following acute stress. Here, we designed a novel comprehensive behavioral test battery in male mice that assesses multiple behavioral dimensions within a sufficiently brief time window to capture acute stress-effects and its temporal profile. Using this battery, we investigated …