Transcriptome Profiling in Autoimmune Diseases

Autoimmune diseases are a group of different inflammatory disorders characterized by systemic or localized inflammation, affecting approximately 0.1–1% of the general population. Several studies suggest that genetic risk loci are shared between different autoimmune diseases and pathogenic mechanisms may also be shared. The strategy of performing differential gene expression profiles in autoimmune disorders has unveiled new transcripts that may be shared among these disorders. Microarray technology and bioinformatics offer the most comprehensive molecular evaluations and it is widely used to understand the changes in gene expression in specific organs or in peripheral blood cells. The major goal of transcriptome studies is the identification of specific biomarkers for different diseases. It is believed that such knowledge will contribute to the development of new drugs, new strategies for early diagnosis, avoiding tissue autoimmune destruction, or even preventing the development of autoimmune disease. In this review, we primarily focused on the transcription profiles of three typical autoimmune disorders, including type 1 diabetes mellitus (destruction of pancreatic islet beta cells), systemic lupus erythematosus (immune complex systemic disorder affecting several organs and tissues), and multiple sclerosis (inflammatory and demyelinating disease of the nervous system). © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2014, 2022.

A rare case of central post-stroke pain in a patient with migraine and lacunar infarcts in the medulla oblongata

Studies about headaches associated with acute ischemic stroke in patients suffering from migraine were limited, and therefore we present a clinical case of central post-stroke pain (CPSP) in a 47-year-old woman with migraine and lacunar infarcts in the medulla oblongata and also possible mechanisms of CPSP in patients with migraine. Magnetic resonance imaging of the brain revealed lacunar infarction in the medulla oblongata on the right (vertebral artery basin) and a single focus of gliosis in the parietal lobe on the right. Magnetic resonance angiography of cerebral vessels showed the fetal type of structure of both posterior cerebral arteries. This clinical case is a complex clinical situation of a combination of secondary headaches (post-stroke) in a patient with a primary headache (migraine), which was successfully treated by the combined administration of first-line drugs for the treatment of neuropathic pain in a patient with lacunar infarcts in the medulla oblongata. The treatment of CPSP is a difficult task due to the insufficiently unexplored mechanisms of development, the most effective approaches are those aimed at reducing the increased excitability of neurons.Copyright © 2023, Indian Association of Biomedical Scientists. All rights reserved.

Microglia activation and neuronal alterations in retinas from COVID-19 patients: correlation with clinical parameters.

BACKGROUND: Different ocular alterations have been described in patients with coronavirus disease 2019 (COVID-19). Our aim was to determine whether COVID-19 affected retinal cells and establish correlations with clinical parameters. METHODS: Retinal sections and flat-mount retinas from human donors with COVID-19 (n = 16) and controls (n = 15) were immunostained. The location of angiotensin-converting enzyme 2 (ACE2) and the morphology of microglial cells, Müller cells, astrocytes, and photoreceptors were analyzed by confocal microscopy. Microglial quantification and the area occupied by them were measured. Correlations among retinal and clinical parameters were calculated. RESULTS: ACE2 was mainly located in the Müller cells, outer segment of cones and retinal pigment epithelium. Cell bodies of Müller cells in COVID-19 group showed greater staining of ACE2 and cellular retinaldehyde-binding protein (CRALBP). The 81.3% of COVID-19 patients presented disorganization of honeycomb-like pattern formed by Müller cells. Gliosis was detected in 56.3% of COVID-19 patients compared to controls (40%) as well as epiretinal membranes (ERMs) or astrocytes protruding (50%). Activated or ameboid-shape microglia was the main sign in the COVID-19 group (93.8%). Microglial migration towards the vessels was greater in the COVID-19 retinas (P < 0.05) and the area occupied by microglia was also reduced (P < 0.01) compared to control group. Cone degeneration was more severe in the COVID-19 group. Duration of the disease, age and respiratory failure were the most relevant clinical data in relation with retinal degeneration. CONCLUSIONS: The retinas of patients with COVID-19 exhibit glial activation and neuronal alterations, mostly related to the inflammation, hypoxic conditions, and age.

Astrocytes and the Psychiatric Sequelae of COVID-19: What We Learned from the Pandemic.

COVID-19, initially regarded as specific lung disease, exhibits an extremely broad spectrum of symptoms. Extrapulmonary manifestations of the disease also include important neuropsychiatric symptoms with atypical characteristics. Are these disturbances linked to stress accompanying every systemic infection, or are due to specific neurobiological changes associated with COVID-19? Evidence accumulated so far indicates that the pathophysiology of COVID-19 is characterized by systemic inflammation, hypoxia resulting from respiratory failure, and neuroinflammation (either due to viral neurotropism or in response to cytokine storm), all affecting the brain. It is reasonable to hypothesize that all these events may initiate or worsen psychiatric and cognitive disorders. Damage to the brain triggers a specific type of reactive response mounted by neuroglia cells, in particular by astrocytes which are the homeostatic cell par excellence. Astrocytes undergo complex morphological, biochemical, and functional remodeling aimed at mobilizing the regenerative potential of the central nervous system. If the brain is not directly damaged, resolution of systemic pathology usually results in restoration of the physiological homeostatic status of neuroglial cells. The completeness and dynamics of this process in pathological conditions remain largely unknown. In a subset of patients, glial cells could fail to recover after infection thus promoting the onset and progression of COVID-19-related neuropsychiatric diseases. There is evidence from post-mortem examinations of the brains of COVID-19 patients of alterations in both astrocytes and microglia. In conclusion, COVID-19 activates a huge reactive response of glial cells, that physiologically act as the main controller of the inflammatory, protective and regenerative events. However, in some patients the restoration of glial physiological state does not occur, thus compromising glial function and ultimately resulting in homeostatic failure underlying a set of specific neuropsychiatric symptoms related to COVID-19.

Retinas of human donors with COVID-19 disease show morphological alterations and signs of inflammation including glial activation

Purpose : Different signs of inflammation have been described in the brains of COVID-19 patients. In the retina, the fundus eye exam of these patients shows cotton wool spots, microhemorrhages, and a decrease in vascular density. However, morphological alterations of retinal cells in these patients are unknown. Thus, the aim was to analyze the morphological changes of the retinal cells from human donors with COVID-19 to establish several stages of response to damage in these cells and to define correlations with clinical parameters. Methods : The retinas of human donors with COVID-19 (n = 16) and control subjects (n = 12) obtained from the General University Hospital Consortium of Valencia were analyzed. Immunohistochemical stainings were performed on transversal sections or flat-mount retinas to study photoreceptors, microglial cells, Müller cells, astrocytes, and the presence of ACE2. TUNEL assays and confocal microscopy imaging were carried out. Correlations were calculated between retinal and clinical parameters. Results : Mean age of COVID-19 and control group were 80±10 and 70±8 years respectively. Müller cells, outer segment of cones and retinal pigment epithelium presented ACE2 staining. Larger staining of ACE2 and CRALBP was observed in cell bodies of Müller cells in COVID group. Disorganization of honeycomb-like pattern formed by Müller cells in the outer nuclear layer and disruption of external limiting membrane was found in the 81.3% of COVID patients. The 56.3% of COVID patients showed gliosis compared to controls (40%). COVID-19 retinas also presented epiretinal membranes and astrocytes protruding to vitreous humor. The 93.8% of COVID-19 patients had activated or ameboid-shape microglia. Microglial nodules around vessels and a reduction of the area occupied by microglia in these retinas were observed. COVID-19 group showed a more severe degeneration of cones. Cone degeneration correlated with Müller cell activation. Age of COVID patients correlated inversely with total retinal degeneration. Conclusions : Morphological alterations in the cone photoreceptors as well as glial activation showing an inflammatory state of the retina were observed in COVID-19 patients.

Disseminated TB in the Setting of COVID-19 Infection- a Cause or a Consequence?

Introduction: Tuberculosis is a deadly infection, which can lead to disseminated TB in children in the presence of risk factors like low host immunity, concurrent infections, etc. This led us to wonder about the relationship between a common killer infection like TB and Coronavirus disease 2019 (COVID-19) and how the disease pattern will present in the pediatric age group. Case Description: We report a case of a 14-year-old male child who was a known case of childhood TB meningitis and hydrocephalus;treated with VP shunt, who recently presented with disseminated TB/TB flare up, causing TB meningitis, TB peritonitis, and pulmonary TB. On investigation, the patient was positive for COVID antibodies, multisystem involvement, lymphopenia and highly raised inflammatory markers suggesting it to be a case of MIS-C induced TB dissemination. He was started on anti-tubercular treatment (ATT), steroids, and supportive treatment, while he never required intravenous immunoglobulin (IVIG). His condition subsequently improved over a few days and he was discharged on ATT and antiepileptics. Discussion: COVID-19 has been reported to be associated with other infections of the respiratory system. Few studies in adults have established a connection between the progression of TB following COVID-19 infection. The link between TB and COVID-19 is mostly bi-directional. The temporary immunosuppression caused by tuberculosis may lead to increased predisposition to COVID-19 infection, while COVID may, in turn, also increase susceptibility to TB infection due to substantial depletions in T-cell lymphocyte counts, promoting the development of active TB in patients with latent TB. Conclusion: In this case report, the child recovered only with corticosteroids and supportive care, with no requirement of immunoglobulins or intensive care after a few days and showing almost a complete recovery. This is an important point to be considered when exploratory therapy is considered for TB with MIS-C. Hence, a better understanding of the pathogenic mechanism of the disease may help in defining the appropriate interventions required for specific cases. USG abdomen showing moderate ascites with few thick internal septations (Red arrow) MRI Brain showing communicating hydrocephalus with dilated lateral and third ventricles (Red star) and an ill-defined area of non-diffusion restricting T2 FLAIR hyperintensity in the right ganglio-capsular region of the brain- likely gliosis (Red arrow).

The 43rd Annual Meeting of the Canadian College of Neuropsychopharmacology November 4, 2021

OVERVIEW OF EVENTS 10:30 am Opening of Meeting 10:45 am Opening Remarks - Dr. Jeff Daskalakis, CCNP President 10:50 am Introduction - Dr. Cecilia Flores, CCNP Vice-President 11:00 am CCNP 2020 Young Investigator Award Presentation Caroline Ménard, PhD, Department of Psychiatry & Neuroscience, Université Laval: "Sex-specific vascular alterations and biomarkers underlie stress responses in mice mirrored in human depression" 11:50 am CCNP Next Generation Awardee Andrea H. Pantoja Urban, MSc, Integrated Program in Neuroscience, McGill University: "Short and long-term effects of social defeat stress in adolescent female mice" 12:05 pm CCNP Next Generation Awardee Orna Issler, PhD, Department of Neuroscience, Mount Sinai:"The sex-specific role for long noncoding RNAs in depression: from genome-wide patterns to behavioral readout" 12:20 pm Lunch/Break 12:50 pm CCNP 2020 Heinz Lehmann Award Presentation Martin Alda, MD, FRCPC, Department of Psychiatry, Dalhousie University: "Personalized long-term treatment of bipolar disorder" 1:40 pm CCNP Next Generation Awardee Mikaela K Dimick, BA, Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health: "Cerebral blood flow and core mood symptoms in youth bipolar disorder: evidence for region-symptom specificity" 1:55 pm CCNP Next Generation Awardee Sneha Chenji, PhD, Department of Psychiatry & Pediatrics, University of Calgary: "The effect of rTMS treatment on cortico-striatal-thalamo-cortical (CSTC) circuit connectivity in Tourette's syndrome: a pilot study" 2:10 pm Break 2:20 pm CCNP 2020 Innovations in Neuropsychopharmacology Award Presentation Jeffrey Meyer, MD, PhD, FRCPC, Department of Psychiatry, University of Toronto: "Imaging markers of gliosis and monoamine oxidase in major depressive disorder: implications for personalized prevention and treatment" 3:10 pm CCNP Next Generation Awardee Jasmine D. Cakmak, MSc, Neuroscience, Western University: "The functional and structural consequences of aberrant microglial activity in major depressive disorder" 3:25 pm CCNP Next Generation Awardee Kayla D. Stone, PhD, Department of Psychiatry, University of Calgary: "Dorsolateral prefrontal cortex neurometabolite concentrations in pediatric mild traumatic brain injury" 3:40 pm Break 3:50 pm Keynote Speaker Rémi Quirion, OC, CQ, PhD, FRSC, Chief Scientist of Quebec, Ministry of Economy & Innovation: "A less well travelled road: from neuroscientist to chief scientist and then came COVID-19" 4:50 pm Closing Remarks - Dr. Cecilia Flores, CCNP Vice President Acknowledgments: In keeping with CMA guidelines, program content and selection of speakers are the responsibility of the planning committee. Methods: Here, we characterized the enduring changes in histone modifications in the NAcc of mice exposed to chronic social defeat stress (CSDS), a validated model for the study of depression-like behaviours that separates mouse populations into susceptible (SUS) and resilient (RES) based on a social interaction test (SIT). Tissue from the NAcc of control, SUS, and RES mice was collected either 24 hours or 4 weeks after the SIT and processed for histone profiling via mass spectrometry. From the Department of Psychiatry, University of Alberta, Edmonton, AB, Canada (Yap, Luki, S. Hanstock, Lirette, Zhaoa, Aitchison, Le Melledo);the Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada (Aitchison);the Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada (Aitchison);the Edmonton Mood and Anxiety Disorders Program, University of Alberta Hospital, Edmonton, AB, Canada (Aitchison);the Department of Biomedical Engineering, University of Alberta, Edmonton, AB, Canada (C. Hanstock, Seres);and the Royal Alexandra Hospital, Edmonton, AB, Canada (Shandro).

Evidence of Ischemic Stroke in Pediatric Patient with Post-COVID-19 Syndrome

Objective: Stroke has been reported to be a potential neurological complication of COVID-19 infection in adults, however, only a few reports have been made in the pediatric population. We describe a case of a 12-year-old female with post-COVID-19 syndrome who was found to have an ischemic stroke on MRI as well as positive for lupus anticoagulant. Background: COVID-19 has been documented to potentiate a prothrombotic and proinflammatory state. It is postulated this occurs via endothelial cell disruption and clotting cascade activation. However, cases have reported the presence of prothrombotic antibodies in patients with COVID-19 infections. The persistent presence of these antibodies has important clinical implications, including an increased thrombotic risk. Design/Methods: Chart review Results: A 12-year-old female with history of migraines presented to the neurology clinic for increased frequency and severity of headaches. Patient reported to have COVID-19 infection one year prior with symptoms of fatigue, arthralgias, sore throat, and headaches. Following infection, patient had resolution of most symptoms but continued having increased headaches and difficulty concentrating. Headaches have been occurring multiple times per week, lasting hours to days, and are associated with nausea, vomiting, and photophobia. Patient has no focal neurological deficits. Brain MRI showed small focal encephalomalacia with surrounding gliosis and volume loss in the anterior right basal ganglia and adjacent external capsule consistent with a small chronic infarct. On thrombophilia work-up patient was positive for lupus anticoagulant and had a heterozygous MTHFR variant. Patient was started on baby aspirin and her headaches have been controlled with prophylactic co-enzyme Q-10 and naproxen. Conclusions: Due to the known prothrombotic risk of COVID-19 infections, there should be a high index of suspicion for stroke symptoms among pediatric patients with COVID-19. Improved clinical surveillance and increased screening for prothrombotic antibodies could ensure better outcomes, including timely treatment and prevention of complications.