Raman spectral analysis of the brainstem and responses of neuroglia and cytokines in whole-body gamma-irradiated rats after administration of aminothiol-based radioprotector GL2011

The search for an effective and non-toxic radioprotector is ongoing. We tested a novel, natural aminothiol-based radioprotector, GL2011, that was applied 30 min, 3 h or 6 h after the exposure of male albino Wistar rats to a 6.7 Gy mild dose of gamma radiation. The molecular signatures of radioprotection were investigated with Raman microspectroscopy of brainstem tissue samples. Morphological changes and activation of astrocytes and microglia were assessed by immunohistochemistry. Global markers of neuroinflammation were followed by ELISA to monitor blood plasma levels of proinflammatory (IL-6 and TNF-α) and anti-inflammatory (IL-10) cytokines. A thirty-day follow-up determined survival of unprotected animals 37.5%. A survival increase was observed after radioprotection (75%, irrespective of the time of application). Raman spectra revealed a slightly deleterious effect of radiation on nucleic acids in surviving animals that was mitigated with the radioprotector, as GL2011 preserved the morphology of both astrocytes and microglia, with reduced microglial infiltration. Cytokine assessment revealed an immunomodulatory effect of the novel radioprotector. The overall results point out the positive effects of a single dose of GL2011 applied at different times. The molecular and cellular changes in the brainstem indicate that the radioprotector applied after radiation conferred better protection, which underlines its translation to cure radiation accidents

Increased survival after irradiation followed by regeneration of bone marrow stromal cells with a novel thiol-based radioprotector

Aim To investigate the survival of laboratory rats after irradiation and to study the cellularity of their bone marrow and the multipotential mesenchymal stem cells (BM-MSCs) in groups treated with or without a new thiol-based radioprotector (GM2011) Methods Animals were irradiated by a Cobalt gamma source at 6.7 Gy. Treated animals were given i.p. GM2011 30 minutes before and 3 and 7 hours after irradiation. Controls consisted of sham irradiated animals without treatment and animals treated without irradiation. After 30 days post-irradiation, animals were sacrificed and bone marrow cells were prepared from isolated femurs. A colony forming unit-fibroblast (CFU-F) assay was performed to obtain the number of BM-MSCs. Results In the treated group, 87% of animals survived, compared to only 30% in the non-treated irradiated group. Irradiation induced significant changes in the bone marrow of the treated rats (total bone marrow cellularity was reduced by similar to 60% - from 63 to 28 cells x10(6)/femur and the frequency of the CFU-F per femur by similar to 70% - from 357 to 97), however GL2011 almost completely prevented the suppressive effect observed on day 30 post-irradiation (71 cells x 10(6)/femur and 230 CFU-F/femur). Conclusion Although the irradiation dosage was relatively high, GL2011 acted as a very effective new radioprotector. The recovery of the BN-MSCs and their counts support the effectiveness of the studied radioprotector

Effect of enriched environment on serotonin and RNA editing of serotonin 2C receptor is specific for brain regions and mouse strains

Serotonin neurotransmission is sensitive to environmental stimuli. Serotonin receptor 2C (HTR2C) undergoes dynamic A-to-I editing that fine-tunes cell response to serotonin and is altered in depressed suicide victims and by pharmacological treatments. We aimed to explore a mediating role of Htr2c mRNA editing in response to enriched environment and factors involved in this response. Three-week-old BALB/c and C57BL/6 male mice were housed in enriched and standard conditions for four weeks. Htr2c mRNA editing pattern and expression, serotonin level and expression of Adar and Adarb1 mRNAs (coding enzymes catalyzing A-to-I editing) and Snord115 RNA (regulating Htr2c mRNA alternative splicing and editing) were measured in prefrontal cortex (PFC) and hippocampus (HC), brain regions implicated in suicidal behavior. BALB/c mice, a “stress-sensitive” strain due to genetically determined lower serotonin level, responded to enriched conditions by adapting the Htr2c editing pattern to a slight serotonin decrease in PFC and a significant increase in HC. C57BL/6 mice, a “stress-resilient” strain, responded to enriched environment by increasing the serotonin level and changing Adar and Adarb1 mRNAs expression in HC, and without changes in PFC. Our findings suggest that the enriched environment effect on the serotonin level and a mediating role of Htr2c mRNA editing in PFC depend on the genetic background and its interactions with the environment. On the other hand, changes in HC are primarily driven by enriched environment. Our results imply usefulness of enriched environment paradigm for understanding interactions of genetic and environmental factors underlying suicidal behavior, which might improve psychological treatments.BOOK OF ABSTRACTS: 8th CONGRESS OF SERBIAN NEUROSCIENCE SOCIETY with international participation 31 May – 2 June 2023. Belgrade, Serbi

Decreased Expression of Alpha1 Subunit of Na(+)/K+-Atpase in the Als Rat Brain

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Decreased Expression of Alpha1 Subunit of Na(+)/K+-Atpase in the Als Rat Brain

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Tenascins and inflammation in disorders of the nervous system

In vitro and in vivo studies on the role of tenascins have shown that the two paradigmatic glycoproteins of the tenascin family, tenascin-C (TnC) and tenascin-R (TnR) play important roles in cell proliferation and migration, fate determination, axonal pathfinding, myelination, and synaptic plasticity. As components of the extracellular matrix, both molecules show distinct, but also overlapping dual functions in inhibiting and promoting cell interactions depending on the cell type, developmental stage and molecular microenvironment. They are expressed by neurons and glia as well as, for TnC, by cells of the immune system. The functional relationship between neural and immune cells becomes relevant in acute and chronic nervous system disorders, in particular when the blood brain and blood peripheral nerve barriers are compromised. In this review, we will describe the functional parameters of the two molecules in cell interactions during development and, in the adult, in synaptic activity and plasticity, as well as regeneration after injury, with TnC being conducive for regeneration and TnR being inhibitory for functional recovery. Although not much is known about the role of tenascins in neuroinflammation, we will describe emerging knowledge on the interplay between neural and immune cells in autoimmune diseases, such as multiple sclerosis and polyneuropathies. We will attempt to point out the directions of experimental approaches that we envisage would help gaining insights into the complex interplay of TnC and TnR with the cells that express them in pathological conditions of nervous and immune systems.MESRS [III41005, ON 173035, ON 173013]; German Research Foundation; New Jersey Commission for Spinal Cord Research; Li Ka-Shing Foundatio

Tenascins and inflammation in disorders of the nervous system

In vitro and in vivo studies on the role of tenascins have shown that the two paradigmatic glycoproteins of the tenascin family, tenascin-C (TnC) and tenascin-R (TnR) play important roles in cell proliferation and migration, fate determination, axonal pathfinding, myelination, and synaptic plasticity. As components of the extracellular matrix, both molecules show distinct, but also overlapping dual functions in inhibiting and promoting cell interactions depending on the cell type, developmental stage and molecular microenvironment. They are expressed by neurons and glia as well as, for TnC, by cells of the immune system. The functional relationship between neural and immune cells becomes relevant in acute and chronic nervous system disorders, in particular when the blood brain and blood peripheral nerve barriers are compromised. In this review, we will describe the functional parameters of the two molecules in cell interactions during development and, in the adult, in synaptic activity and plasticity, as well as regeneration after injury, with TnC being conducive for regeneration and TnR being inhibitory for functional recovery. Although not much is known about the role of tenascins in neuroinflammation, we will describe emerging knowledge on the interplay between neural and immune cells in autoimmune diseases, such as multiple sclerosis and polyneuropathies. We will attempt to point out the directions of experimental approaches that we envisage would help gaining insights into the complex interplay of TnC and TnR with the cells that express them in pathological conditions of nervous and immune systems.MESRS [III41005, ON 173035, ON 173013]; German Research Foundation; New Jersey Commission for Spinal Cord Research; Li Ka-Shing Foundatio