Optogenetic Stimulation of the Axons of Visual Cortex and Hippocampus Pyramidal Neurons in Living Brain Slices

Neuroscience and Behavioral Physiology - Widening and deepening our understanding of how the brain works requires constant improvements not only in methods of recording neuron activity, but also...     

Serotonin and Dopamine in Biological Models of Depression

Neuroscience and Behavioral Physiology - Depression in the biological models considered here can be split into two opposite patterns of changes in serotonin and dopamine levels, corresponding to...     

Neonatal Proinflammatory Stress and Deficit of Induction of Long-Term Potentiation in the Hippocampus in Rats: Gender Differences

Neuroscience and Behavioral Physiology - The characteristics of long-term potentiation (LTP) in field CA1 of living hippocampal slices from rats aged 17–33 days were studied after neonatal...     

Efficacy of Botulinum Therapy in Correcting the Level of Pain Syndrome and Quality of Life in Patients with Cervical Dystonia

Neuroscience and Behavioral Physiology - Objectives. To assess the severity of pain syndrome, emotional status, and quantitative levels of humoral serotonin in patients with cervical dystonia (CD)...     

Association of Chronotype,Road Traffic Accidents,and Polymorphisms in Genes Linked with the Biological Clock and the Dopaminergic System

Neuroscience and Behavioral Physiology - Objective. To study the association between single-nucleotide polymorphisms (SNP) of the RORA (rs1159814), CLOCK (rs12649507), PER3 (rs2640909), NPSR1...     

Use of Anchoring Motifs to Support the Central and Peripheral Locations of Opsins in Optogenetics

Neuroscience and Behavioral Physiology - One version of the optogenetic prosthetization of the degenerative retina is an approach based on creation of an ON/OFF receptive field for ganglion neurons...     

Learning with Reinforcement: the Role of Immediate Feedback and the Internal Model of the Situation

Neuroscience and Behavioral Physiology - Human behavior in conditions of partial indeterminacy of the outcome is characterized by correspondence between the frequency of actions and the probability...     

Comparative Characteristics of the Expression of Inducible NO Synthase in the Hippocampus of Humans and Experimental Animals

Neuroscience and Behavioral Physiology - Objective: To study the characteristics of the expression of inducible NO synthase (iNOS) in hippocampal fields CA1 and CA3 in adult male humans and adult...     

Dexamethasone turns tumor antigen-presenting cells into tolerogenic dendritic cells with T cell inhibitory functions

BackgroundDendritic cells (DCs) are usually immunogenic, but they are also capable of inducing tolerance under anti-inflammatory conditions. Immunotherapy based on autologous DCs loaded with an allogeneic melanoma cell lysate (TRIMEL/DCs) induces immunological responses and increases melanoma patient survival. Glucocorticoids can suppress DC maturation and function, leading to a DC-mediated inhibition of T cell responses.MethodsThe effect of dexamethasone, a glucocorticoid extensively used in cancer therapies, on TRIMEL/DCs phenotype and immunogenicity was examined.ResultsDexamethasone induced a semi-mature phenotype on TRIMEL/DC with low maturation surface marker expressions, decreased pro-inflammatory cytokine induction (IL-1β and IL-12) and increased release of regulatory cytokines (IL-10 and TGF-β). Dexamethasone-treated TRIMEL/DCs inhibited allogeneic CD4⁺ T cell proliferation and cytokine release (IFNγ, TNF-α and IL-17). Co-culturing melanoma-specific memory tumor-infiltrating lymphocytes with dexamethasone-treated TRIMEL/DC inhibited proliferation and effector T cell activities, including cytokine secretion and anti-melanoma cytotoxicity.ConclusionsThese findings suggest that dexamethasone repressed melanoma cell lysate-mediated DC maturation, generating a potent tolerogenic-like DC phenotype that inhibited melanoma-specific effector T cell activities. These results suggest that dexamethasone-induced immunosuppression may interfere with the clinical efficacy of DC-based melanoma vaccines, and must be taken into account for optimal design of cellular therapy against cancer.