Chronic nicotine treatment decreases LPS signaling through NF-κB and TLR-4 modulation in the hippocampus.

The hippocampus is a brain region that is rich in nicotinic acetylcholine receptors (nAChRs), especially the α7 subtype. The hippocampus is severely affected in disorders that have a neuroinflammatory component, such as Alzheimer's disease, Parkinson's disease, and schizophrenia. Previous studies demonstrated both in vivo and in vitro that nicotine inhibits immunological responses, including those that are triggered by the inflammatory agent lipopolysaccharide (LPS), the endotoxin of Gram-negative bacteria. The present study investigated whether chronically administered nicotine interferes with the nuclear binding of nuclear factor-κB (NF-κB) and the expression of LPS-induced inflammatory response genes. The results indicated that chronic nicotine administration (0.1mg/kg, s.c., 14days) inhibited the LPS-induced nuclear binding of NF-κB and mRNA expression levels of Tnf, Il1b, Nos2, and Tlr4. The presence of both the selective α7 nAChR antagonist methyllycaconitine (MLA; 5.0mg/kg i.p., 14days) and the nonselective nAChR antagonist mecamylamine (Meca; 1.0mg/kg, s.c., 14days) reversed the inhibitory effects of nicotine. These results suggest that the chronic activation of α7- and αxßy-containing nAChRs reduces acute inflammatory responses in the brain.

Environmental enrichment protects against stress-induced anxiety: Role of glucocorticoid receptor, ERK, and CREB signaling in the basolateral amygdala.

Environmental enrichment (EE) is an experimental animal model that enhances an animal's opportunity to interact with sensory, motor, and social stimuli, compared to standard laboratory conditions. A prominent benefit of EE is the reduction of stress-induced anxiety. The relationship between stress and the onset of anxiety-like behavior has been widely investigated in experimental research, showing a clear correlation with structural changes in the hippocampus and basolateral amygdala (BLA). However, the mechanisms by which EE exerts its protective roles in stress and anxiety remain unclear, and it is not known whether EE reduces the effects of acute stress on animal behavior shortly following the cessation of stress. We found that EE can prevent the emergence of anxiety-like symptoms in rats measured immediately after acute restraint stress (1 h) and this effect is not due to changes in systemic release of corticosterone. Rather, we found that stress promotes a rapid increase in the nuclear translocation of glucocorticoid receptor (GR) in the BLA, an effect prevented by previous EE exposure. Furthermore, we observed a reduction of ERK (a MAPK protein) and CREB activity in the BLA promoted by both EE and acute stress. Finally, we found that EE decreases the expression of the immediate-early gene EGR-1 in the BLA, indicating a possible reduction of neuronal activity in this region. Hyperactivity of BLA neurons has been reported to accompany anxiety-like behavior and changes in this process may be one of the mechanism by which EE exerts its protective effects against stress-induced anxiety.

Environmental modulation of ethanol-induced locomotor activity: Correlation with neuronal activity in distinct brain regions of adolescent and adult Swiss mice.

Drug abuse is a concerning health problem in adults and has been recognized as a major problem in adolescents. Induction of immediate-early genes (IEG), such as c-Fos or Egr-1, is used to identify brain areas that become activated in response to various stimuli, including addictive drugs. It is known that the environment can alter the response to drugs of abuse. Accordingly, environmental cues may trigger drug-seeking behavior when the drug is repeatedly administered in a given environment. The goal of this study was first to examine for age differences in context-dependent sensitization and then evaluate IEG expression in different brain regions. For this, groups of mice received i.p. ethanol (2.0 g/kg) or saline in the test apparatus, while other groups received the solutions in the home cage, for 15 days. One week after this treatment phase, mice were challenged with ethanol injection. Acutely, ethanol increased both locomotor activity and IEG expression in different brain regions, indistinctly, in adolescent and adult mice. However, adults exhibited a typical context-dependent behavioral sensitization following repeated ethanol treatment, while adolescent mice presented gradually smaller locomotion across treatment, when ethanol was administered in a paired regimen with environment. Conversely, ethanol-treated adolescents expressed context-independent behavioral sensitization. Overall, repeated ethanol administration desensitized IEG expression in both adolescent and adult mice, but this effect was greatest in the nucleus accumbens and prefrontal cortex of adolescents treated in the context-dependent paradigm. These results suggest developmental differences in the sensitivity to the conditioned and unconditioned locomotor effects of ethanol.

Role of IgG(T) and IgGa isotypes obtained from arachnidic antivenom to neutralize toxic activities of Loxosceles gaucho, Phoneutria nigriventer and Tityus serrulatus venoms.

The ability of IgG(T) and IgGa subclasses--isolated by liquid chromatography from equine arachnidic antivenom (AAV)-to neutralize toxic activities of Loxosceles gaucho, Phoneutria nigriventer and Tityus serrulatus venoms as well as to remove venom toxins from circulation was investigated. These subclasses showed similar antibody titers against L. gaucho, P. nigriventer and T. serrulatus venoms, and by immunoblotting few differences were observed in the recognition pattern of venom antigens. IgG(T) and IgGa neutralized 100% lethality induced by L. gaucho and 50% of P. nigriventer venom, but IgGa failed to neutralize T. serrulatus venom, in contrast to IgG(T). Both subclasses neutralized local reactions and dermonecrosis induced by L. gaucho venom in rabbits. In mice, IgG(T) and IgGa partially neutralized the edematogenic activity induced by P. nigriventer and T. serrulatus venoms, but only IgG(T) neutralized (ca. 81%) the nociceptive activity induced by T. serrulatus venom. Both subclasses failed to neutralize nociceptive activity induced by P. nigriventer venom. IgG(T) reduced the serum venom levels of animals injected with L. gaucho, P. nigriventer or T. serrulatus venoms, while IgGa solely reduced L. gaucho and P. nigriventer venoms levels. Our results demostrate that IgG(T) and IgGa subclasses neutralize toxic activities induced by P. nigriventer, T. serrulatus and L. gaucho venoms with different efficacies, as well as depurate these venoms from circulation.

Chronic unpredictable stress exacerbates lipopolysaccharide-induced activation of nuclear factor-kappaB in the frontal cortex and hippocampus via glucocorticoid secretion.

Although the anti-inflammatory actions of glucocorticoids (GCs) are well established in the periphery, these stress hormones can increase inflammation under some circumstances in the brain. The transcription factor nuclear factor-kappaB (NF-kappaB), which is inhibited by GCs, regulates numerous genes central to inflammation. In this study, the effects of stress, GCs, and NMDA receptors on lipopolysaccharide (LPS)-induced activation of NF-kappaB in the brain were investigated. One day after chronic unpredictable stress (CUS), nonstressed and CUS rats were treated with saline or LPS and killed 2 h later. CUS potentiated the increase in LPS-induced activation of NF-kappaB in frontal cortex and hippocampus but not in the hypothalamus. This stress effect was blocked by pretreatment of rats with RU-486, an antagonist of the GC receptor. MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate], an NMDA receptor antagonist, also reduced the effect of LPS in all three brain regions. However, the combined antagonism of both GC and NMDA receptors produced no further reduction in NF-kappaB activation when compared with the effect of each treatment alone. Our results indicate that stress, via GC secretion, can increase LPS-induced NF-kappaB activation in the frontal cortex and hippocampus, agreeing with a growing literature demonstrating proinflammatory effects of GCs.

Role of IgG(T) and IgGa isotypes obtained from arachnidic antivenom to neutralize toxic activities of Loxosceles gaucho, Phoneutria nigriventer and Tityus serrulatus venoms

The ability of IgG(T) and IgGa subclasses—isolated by liquid chromatography from equine arachnidic antivenom (AAV)—to neutralize toxic activities of Loxosceles gaucho, Phoneutria nigriventer and Tityus serrulatus venoms as well as to remove venom toxins from circulation was investigated. These subclasses showed similar antibody titers against L. gaucho, P. nigriventer and T. serrulatus venoms, and by immunoblotting few differences were observed in the recognition pattern of venom antigens. IgG(T) and IgGa neutralized 100% lethality induced by L. gaucho and 50% of P. nigriventer venom, but IgGa failed to neutralize T. serrulatus venom, in contrast to IgG(T). Both subclasses neutralized local reactions and dermonecrosis induced by L. gaucho venom in rabbits. In mice, IgG(T) and IgGa partially neutralized the edematogenic activity induced by P. nigriventer and T. serrulatus venoms, but only IgG(T) neutralized (ca. 81%) the nociceptive activity induced by T. serrulatus venom. Both subclasses failed to neutralize nociceptive activity induced by P. nigriventer venom. IgG(T) reduced the serum venom levels of animals injected with L. gaucho, P. nigriventer or T. serrulatus venoms, while IgGa solely reduced L. gaucho and P. nigriventer venoms levels. Our results demostrate that IgG(T) and IgGa subclasses neutralize toxic activities induced by P. nigriventer, T. serrulatus and L. gaucho venoms with different efficacies, as well as depurate these venoms from circulation.