Follow-up of cognitive impairment and inflammatory profile in individuals with mild COVID-19.

Individuals who experience mild COVID-19 can suffer from long-lasting cognitive symptoms. Notably, 26% of these individuals experience difficulties with visuospatial abilities six months after infection. However, among those who initially exhibited visuoconstructive impairments, 66% showed improvement or complete reversal over time.

Selective visuoconstructional impairment following mild COVID-19 with inflammatory and neuroimaging correlation findings.

People recovered from COVID-19 may still present complications including respiratory and neurological sequelae. In other viral infections, cognitive impairment occurs due to brain damage or dysfunction caused by vascular lesions and inflammatory processes. Persistent cognitive impairment compromises daily activities and psychosocial adaptation.

Neurochemical abnormalities in the hippocampus of male rats displaying audiogenic seizures, a genetic model of epilepsy.

Background: Epilepsy is a disorder characterized by recurrent seizures that affects 1% of the population. However, the neurochemical alterations observed in epilepsy are not fully understood. There are different animal models of epilepsy, such as genetic or drug induced.

HLA-DRB1 GENE POLYMORPHISMS IN PEDIATRIC PATIENTS WITH TYPE 1 AUTOIMMUNE HEPATITIS AND TYPE 1 AUTOIMMUNE HEPATITIS OVERLAP SYNDROME WITH AUTOIMMUNE CHOLANGITIS.

Background: Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease associated with a loss of immunological tolerance to self-antigens. Susceptibility to AIH is partially determined by the presence of genes related to human leukocyte antigen (HLA), mainly allelic variants of DRB1.

Objective: The purpose of this study was to investigate the frequencies of the polymorphisms in HLA-DRB1 gene in children and adolescents with type 1 AIH and type 1 AIH overlap syndrome with autoimmune cholangitis (overlap syndrome, OS) in comparison to healthy sex and age-matched individuals (control group).

Automated evaluation of hippocampal subfields volumes in mesial temporal lobe epilepsy and its relationship to the surgical outcome.

The International League Against Epilepsy (ILAE) classification system for hippocampal sclerosis (HS) is based on location and extent of hippocampal neuron loss. Specific subgroups have a better surgical prognosis. Automated hippocampal subfields segmentation and volume measure could be obtained from high field MRI and used to pre-operatively classify the patients in ILAE subgroups to define best candidates for surgery.

Plasma and cerebrospinal fluid levels of cytokines as disease markers of neurologic manifestation in long-term HTLV-1 infected individuals.

Aim: The aim of this study is to evaluate the presence of a particular immunological profile in individuals long-term infected with HTLV-1, followed presenting different clinical courses.

Materials & Methods: Forty-eight individuals were evaluated for 19 cytokines analyzed in cerebrospinal fluid and plasma of patients with HTLV-1 presenting with and without neurological symptoms.

Results: Proinflammatory cytokines and the chemokine ligand 11 (ITAC/CXCL11) were increased in individuals with HTLV-1 coursing with neurological symptoms.

Brain Metabolism Changes in Patients Infected with HTLV-1.

The Human T-cell leukemia virus type-I (HTLV-1) is the causal agent of HTLV-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP). HAM/TSP is the result of demyelination and cell death in the spinal cord and disruption of the blood-brain barrier (BBB), mediated by a virus-induced inflammatory response. In this study, we applied Positron Emission Tomography with 18F-fluordeoxyglucose (18F-FDG PET) to evaluate brain metabolism in a group of 47 patients infected with HTLV-1, and 18 healthy controls.

Circulating CD4 and CD8 T cells expressing pro-inflammatory cytokines in a cohort of mesial temporal lobe epilepsy patients with hippocampal sclerosis.

Objective: To compare the proinflammatory and anti-inflammatory cytokine expression profile of CD4(+) and CD8(+) T lymphocytes between drug resistant mesial Temporal Lobe Epilepsy (mTLE) patients and healthy subjects.

Methods: mTLE patients were enrolled at the Neurology Center of Santa Casa de Misericórdia de Belo Horizonte (SCM-BH) and healthy volunteers were selected at Universidade Federal de Minas Gerais. Individuals from both groups accepted to participate in this study and signed an informed consent.

Telomere length is highly inherited and associated with hyperactivity-impulsivity in children with attention deficit/hyperactivity disorder.

Telomere length (TL) is highly heritable, and a shorter telomere at birth may increase the risk of age-related problems. Additionally, a shorter TL may represent a biomarker of chronic stress and has been associated with psychiatric disorders. However, no study has explored whether there is an association between TL and the symptoms of one of the most common neurodevelopmental disorders in childhood: Attention Deficit/Hyperactive Disorder (ADHD).

Analysis of telomere attrition in bipolar disorder.

Background: Telomeres can be considered a marker of biological aging. Studies have suggested that telomere shortening may be associated with aging related diseases and also psychiatric disorders.

Objectives: Investigate whether bipolar disorder (BD) and its clinical specificities are associated with telomere shortening.

Glycine transporters type 1 inhibitor promotes brain preconditioning against NMDA-induced excitotoxicity.

Brain preconditioning is a protective mechanism, which can be activated by sub-lethal stimulation of the NMDA receptors (NMDAR) and be used to achieve neuroprotection against stroke and neurodegenerative diseases models. Inhibitors of glycine transporters type 1 modulate glutamatergic neurotransmission through NMDAR, suggesting an alternative therapeutic strategy of brain preconditioning. The aim of this work was to evaluate the effects of brain preconditioning induced by NFPS, a GlyT1 inhibitor, against NMDA-induced excitotoxicity in mice hippocampus, as well as to study its neurochemical mechanisms.

Association of angiotensin type 2 receptor gene polymorphisms with ureteropelvic junction obstruction in Brazilian patients.

Aim: The angiotensin type 2 (AT2 ) receptor takes part in the process of ureteric bud during kidney development. Therefore, the gene encoding AT2 receptor, the AGTR2 gene located in the X chromosome, is a potential candidate for genetic association with Congenital Anomalies of the Kidney and Urinary Tract (CAKUT). This study aimed to investigate whether AGTR2 gene polymorphisms are associated with CAKUT in general or even with common phenotypes of CAKUT in a Brazilian sample of paediatric patients.

Evaluation of NCS-1, DARPP-32, and neurotrophins in hippocampus and prefrontal cortex in rats submitted to sepsis.

Sepsis is defined as the host's reaction to infection and it is characterized by a systemic inflammatory response with important clinical implications. Central nervous system dysfunction secondary to sepsis is associated with local generation of pro- and anti-inflammatory cytokines, impaired cerebral microcirculation, disturbance of neurotransmitters, apoptosis, and cognitive impairment. It is known that during the process of learning and memory formation several pathways are involved such as dopaminergic and cholinergic systems.

NCS-1 deficiency causes anxiety and depressive-like behavior with impaired non-aversive memory in mice.

Sensing and regulating intracellular levels of calcium are essential for proper cellular function. In neurons, calcium sensing plays important roles in neuronal plasticity, neurotransmitter release, long-term synapse modification and ion channel activity. Neuronal calcium sensor-1 (NCS-1) is a member of the highly conserved neuronal calcium sensor family.

Effects of lamotrigine on behavior, oxidative parameters and signaling cascades in rats exposed to the chronic mild stress model.

The rats were subjected to 40 days of stress protocol, during which the sucrose consumption was assessed in rats chronically treated with lamotrigine (20mg/kg) or with saline. The signaling cascade and oxidative stress parameters were assessed in the brain rat. Both control and stressed rats treated with lamotrigine showed an increase on malondialdehyde equivalents (MDA) in the prefrontal cortex, and that there was also an increase in the amygdala of the control rats treated with lamotrigine.

Sociodemographic characteristics, clinical factors, and genetic polymorphisms associated with Alzheimer's disease.

Objective: Alzheimer's disease (AD) has a multifactorial etiology involving an interaction of genetic and environmental factors. The Apolipoprotein E ε4 (ApoE ε4) is the single most important genetic risk factor for sporadic AD. Our aim was to study the association between sociodemographic, clinical data and gene polymorphisms in patients with sporadic AD in a heterogeneous genomic Brazilian population with low educational levels.

Molecular medicine: a path towards a personalized medicine.

Psychiatric disorders are among the most common human illnesses; still, the molecular and cellular mechanisms underlying their complex pathophysiology remain to be fully elucidated. Over the past 10 years, our group has been investigating the molecular abnormalities in major signaling pathways involved in psychiatric disorders. Recent evidences obtained by the Instituto Nacional de Ciência e Tecnologia de Medicina Molecular (National Institute of Science and Technology - Molecular Medicine, INCT-MM) and others using behavioral analysis of animal models provided valuable insights into the underlying molecular alterations responsible for many complex neuropsychiatric disorders, suggesting that "defects" in critical intracellular signaling pathways have an important role in regulating neurodevelopment, as well as in pathophysiology and treatment efficacy.

Acute low dose of MK-801 prevents memory deficits without altering hippocampal DARPP-32 expression and BDNF levels in sepsis survivor rats.

Sepsis is characterized by an intense inflammatory reaction with potential neurotoxic effects in the central nervous system and damage to memory and learning ability. We assessed the effects of acute low dose of MK-801 on the memory impairment, hippocampal BDNF levels and DARPP-32 expression ten days after sepsis. Under anesthesia, male Wistar rats underwent either cecal ligation and perforation (CLP) or sham.

Downregulation of the cAMP/PKA pathway in PC12 cells overexpressing NCS-1.

It is well known that dopamine imbalances are associated with many psychiatric disorders and that the dopaminergic receptor D₂ is the main target of antipsychotics. Recently it was shown that levels of two proteins implicated in dopaminergic signaling, Neuronal calcium sensor-1 (NCS-1) and DARPP-32, are altered in the prefrontal cortex (PFC) of both schizophrenic and bipolar disorder patients. NCS-1, which inhibits D₂ internalization, is upregulated in the PFC of both patients.

Lack of association of NALCN genetic variants with schizophrenia.

NALCN (sodium leak channel, non-selective) is located on chromosome 13q (suggested linkage region for schizophrenia). We analyzed 21 polymorphisms in 464 schizophrenia subjects, 220 controls subjects and 119 small nuclear families. We observed nominal association with rs9518320 and rs9518331, suggesting that NALCN is not related to schizophrenia risk.

Lack of effects of typical and atypical antipsychotics in DARPP-32 and NCS-1 levels in PC12 cells overexpressing NCS-1.

Background: Schizophrenia is the major psychiatry disorder, which the exact cause remains unknown. However, it is well known that dopamine-mediated neurotransmission imbalance is associated with this pathology and the main target of antipsychotics is the dopamine receptor D2. Recently, it was described alteration in levels of two dopamine signaling related proteins in schizophrenic prefrontal cortex (PFC): Neuronal Calcium Sensor-1 (NCS-1) and DARPP-32.

Inhibitory avoidance task does not change NCS-1 level in rat brain.

Step-down inhibitory avoidance is usually acquired in one single trial, which makes it ideal for studying processes initiated by training, uncontaminated by prior or further trials, rehearsals, or retrievals. Neuronal calcium sensor 1 (NCS-1) is a dopamine receptor interacting protein that has been associated with associative learning and memory. We evaluated whether inhibitory avoidance can alter NCS-1 levels in rat brain.

Early long-term exposure with caffeine induces cross-sensitization to methylphenidate with involvement of DARPP-32 in adulthood of rats.

Chronic ingestion of caffeine causes dependence and sleep disturbance in children and adolescents. In rodents, the administration of caffeine may produce behavioral cross-sensitization to some psychostimulants, such as dopaminergic psychoactive drugs. Methylphenidate (MPH; Ritalin) is a psychostimulant used in pediatric- and adult human populations to manage the symptoms associated with attention-deficit hyperactivity disorder (ADHD).

Cerebral DARPP-32 expression after methylphenidate administration in young and adult rats.

Dopamine may alter the phosphorylation state of DARPP-32 that plays a central role in the dopaminergic neurons biology. Studies have shown that DARPP-32/protein phosphatase 1 cascade is a major target for psychostimulants drugs. Methylphenidate is a psychostimulant that acts blocking the dopamine transporter has been used as an effective treatment for Attention Deficit Hyperactivity Disorder.