Experimenters' sex modulates mouse behaviors and neural responses to ketamine via corticotropin releasing factor.

We show that the sex of human experimenters affects mouse behaviors and responses following administration of the rapid-acting antidepressant ketamine and its bioactive metabolite (2R,6R)-hydroxynorketamine. Mice showed aversion to the scent of male experimenters, preference for the scent of female experimenters and increased stress susceptibility when handled by male experimenters. This human-male-scent-induced aversion and stress susceptibility was mediated by the activation of corticotropin-releasing factor (CRF) neurons in the entorhinal cortex that project to hippocampal area CA1.

Association of complement component 4 with neuroimmune abnormalities in the subventricular zone in schizophrenia and autism spectrum disorders.

An early inflammatory insult is the most recognized risk factor associated with neurodevelopmental psychiatric disorders, even more so than genetic variants. Notably, complement component 4 (C4), a molecule involved in inflammatory responses, has been strongly associated with schizophrenia (SZ) and its role in other neurodevelopmental disorders, such as autism (ASD), is an area of active investigation. However, while C4 in SZ has been implicated in the context of synaptic pruning, little is known about its neuroinflammatory role.

Subcutaneous dirofilariosis in Italy: a diagnostic hypothesis to remind when the anamnesis is misleading.

Subcutaneous parasitic infections are possible matches in routine pathology and can be detected not only in patients coming from or travelling in tropical countries, but also when the anamnesis does not suggest at first worm infestations. Here we report the case of a young man from the north-west of Italy, with a negative anamnesis for travels but the presence of dogs at home, who presented a subcutaneous nodule showing a nematode surrounded by a fibrous capsule; the morphology was suggestive for Dirofilaria repens. Dirofilariosis is a zoonosis caused by D.

Long-term persistence of infectious Zika virus: Inflammation and behavioral sequela in mice.

The neurodevelopmental defects associated with ZIKV infections early in pregnancy are well documented, however the potential defects and long-term consequences associated with milder infections in late pregnancy and perinatal period are less well understood. To model these, we challenged 1 day old (P1) immunocompetent C57BL/6 mice with ZIKV. The animals developed a transient neurological syndrome including unsteady gait, kinetic tremors, severe ataxia and seizures 10-15 days post-infection (dpi) but symptoms subsided after a week, and most animals survived.

Time and frequency dependent changes in resting state EEG functional connectivity following lipopolysaccharide challenge in rats.

Research has shown that inflammatory processes affect brain function and behavior through several neuroimmune pathways. However, high order brain functions affected by inflammation largely remain to be defined. Resting state functional connectivity of synchronized oscillatory activity is a valid approach to understand network processing and high order brain function under different experimental conditions.

Maternal immune activation in rats blunts brain cytokine and kynurenine pathway responses to a second immune challenge in early adulthood.

Maternal immune activation (MIA) with the viral mimic poly I:C provides an established rodent model for studying schizophrenia (SZ) and other human neurodevelopmental disorders. Postnatal infections are additional risk factors in SZ and may cumulatively contribute to the emergence of pathophysiology. Underlying mechanisms may involve metabolites of the kynurenine pathway (KP) of tryptophan degradation, which is readily induced by inflammatory stimuli.

Increased circulating regulatory T cells in medicated people with schizophrenia.

Immunological abnormalities are increasingly reported in people with schizophrenia, but no clear functional biomarkers associated with genetic correlates of the disease have been found. Regulatory T cells (Tregs) are key immunoregulatory cells involved in the control of inflammatory processes and their functions are directly related to the human leucocyte antigen (HLA) gene, which has been implicated in schizophrenia genetic studies. However, there is a lack of studies reporting Treg status in people with schizophrenia.

CD8 T cells promote cytokine responses to stress.

Psychological stress is known to have profound effects on immune function and to promote inflammatory conditions. Elevated circulating levels of cytokines associated with stress are known to increase the risk to several diseases, but little is known about this mechanism. This study assessed the role of T cells on cytokine levels after exposure to stress in the learned helplessness paradigm.

Neonatal adoptive transfer of lymphocytes rescues social behaviour during adolescence in immune-deficient mice.

Accumulating evidence has shown that lymphocytes modulate behaviour and cognition by direct interactions with the central nervous system. Studies have shown that reconstitution by adoptive transfer of lymphocytes from wild type into immune-deficient mice restores a number of neurobehavioural deficits observed in these models. Moreover, it has been shown that these effects are mostly mediated by T lymphocytes.

Quantitative Analysis of Kynurenine Aminotransferase II in the Adult Rat Brain Reveals High Expression in Proliferative Zones and Corpus Callosum.

Kynurenic acid, a metabolite of the kynurenine pathway of tryptophan degradation, acts as an endogenous antagonist of alpha7 nicotinic and NMDA receptors and is implicated in a number of neurophysiological and neuropathological processes including cognition and neurodegenerative events. Therefore, kynurenine aminotransferase II (KAT II/AADAT), the enzyme responsible for the formation of the majority of neuroactive kynurenic acid in the brain, has prompted significant interest. Using immunohistochemistry, this enzyme was localized primarily in astrocytes throughout the adult rat brain, but detailed neuroanatomical studies are lacking.

Reduced kynurenine pathway metabolism and cytokine expression in the prefrontal cortex of depressed individuals.

Background: Neuroinflammatory processes are increasingly believed to participate in the pathophysiology of a number of major psychiatric diseases, including depression. Immune activation stimulates the conversion of the amino acid tryptophan to kynurenine, leading to the formation of neuroactive metabolites, such as quinolinic acid and kynurenic acid. These compounds affect glutamatergic neurotransmission, which plays a prominent role in depressive pathology.

CD4(+) T cells confer anxiolytic and antidepressant-like effects, but enhance fear memory processes in Rag2(-/-) mice.

Accumulating evidence supports a role of T cells in behavioral stress responsiveness. Our laboratory previously reported that lymphocyte deficient Rag2(-/-) mice on a BALB/c background display resilience to maladaptive stress responses when compared with immune competent mice in the predator odor exposure (POE) paradigm, while exhibiting similar behavior in a cued fear-conditioning (FC) paradigm. In the present study, Rag2(-/-) mice on a C57BL/6 background were assessed in the same behavioral paradigms, as well as additional tests of anxiety and depressive-like behavior.

Expansion of brain T cells in homeostatic conditions in lymphopenic Rag2(-/-) mice.

The concept of the brain as an immune privileged organ is rapidly evolving in light of new findings outlining the sophisticated relationship between the central nervous and the immune systems. The role of T cells in brain development and function, as well as modulation of behavior has been demonstrated by an increasing number of studies. Moreover, recent studies have redefined the existence of a brain lymphatic system and the presence of T cells in specific brain structures, such as the meninges and choroid plexus.

Sex-dependent modulation of age-related cognitive decline by the L-type calcium channel gene Cacna1c (Cav 1.2).

Increased calcium influx through L-type voltage-gated calcium channels has been implicated in the neuronal dysfunction underlying age-related memory declines. The present study aimed to test the specific role of Cacna1c (which encodes Cav 1.2) in modulating age-related memory dysfunction.

Dissociation between sickness behavior and emotionality during lipopolysaccharide challenge in lymphocyte deficient Rag2(-/-) mice.

Inflammatory diseases are highly associated with affective disorders including depression and anxiety. While the role of the innate immune system on emotionality has been extensively studied, the role of adaptive immunity is less understood. Considering that chronic inflammatory conditions are mediated largely by maladaptive lymphocyte function, the role of these cells on brain function and behavior during inflammation warrants investigation.

Immune status influences fear and anxiety responses in mice after acute stress exposure.

Significant evidence suggests that exposure to traumatic and/or acute stress in both mice and humans results in compromised immune function that in turn may affect associated brain processes. Additionally, recent studies in mouse models of immune deficiency have suggested that adaptive immunity may play a role during traumatic stress exposure and that impairments in lymphocyte function may contribute to increased susceptibility to various psychogenic stressors. However, rodent studies on the relationship between maladaptive stress responses and lymphocyte deficiency have been complicated by the fact that genetic manipulations in these models may also result in changes in CNS function due to the expression of targeted genes in tissues other than lymphocytes, including the brain.

The outdoor air pollution and brain health workshop.

Accumulating evidence suggests that outdoor air pollution may have a significant impact on central nervous system (CNS) health and disease. To address this issue, the National Institute of Environmental Health Sciences/National Institute of Health convened a panel of research scientists that was assigned the task of identifying research gaps and priority goals essential for advancing this growing field and addressing an emerging human health concern. Here, we review recent findings that have established the effects of inhaled air pollutants in the brain, explore the potential mechanisms driving these phenomena, and discuss the recommended research priorities/approaches that were identified by the panel.

Pollen-specific immunoglobulin E positivity is associated with worsening of depression scores in bipolar disorder patients during high pollen season.

Objective: An association between allergic disease and depression has been consistently reported, but whether the key mediating ingredients are predominantly biological, psychological, or mere artifacts remains unknown. In the current study, we examined a hypothesized relationship between allergen-specific immunoglobulin E (IgE) status and changes in allergy symptoms with worsening in depression scores.

Methods: In patients with recurrent mood disorders, we individually coupled sensitization to specific seasonal aeroallergens (as assessed by allergen-specific IgE) with temporal windows of exposure to aeroallergens (low versus high tree or ragweed pollen counts, measured according to the National Allergy Bureau guidelines).

Effects of the triple monoamine uptake inhibitor DOV 102,677 on alcohol-motivated responding and antidepressant activity in alcohol-preferring (P) rats.

Background:   Concurrent inhibitors of dopamine, norepinephrine, and serotonin uptake have been proposed as novel antidepressants. Given the high comorbidity between alcoholism and depression, we evaluated the activity of DOV 102,677 (DOV) on alcohol-maintained responding and performance in the forced swim test (FST), a model of antidepressant (AD) activity, using alcohol-preferring (P) rats.

Methods:   Following training to lever press for either alcohol (10% v/v) or sucrose (3, 2%, w/v) on a fixed-ratio 4 (FR4) schedule, DOV (1.

Disruption of protein arginine N-methyltransferase 2 regulates leptin signaling and produces leanness in vivo through loss of STAT3 methylation.

Rationale: Arginine methylation by protein N-arginine methyltransferases (PRMTs) is an important posttranslational modification in the regulation of protein signaling. PRMT2 contains a highly conserved catalytic Ado-Met binding domain, but the enzymatic function of PRMT2 with respect to methylation is unknown. The JAK-STAT pathway is proposed to be regulated through direct arginine methylation of STAT transcription factors, and STAT3 signaling is known to be required for leptin regulation of energy balance.

Expression and regulation in the brain of the chemokine CCL27 gene locus.

The chemokine CCL27 has chemoattractant properties for memory T cells and has been implicated in skin allergic reactions. The present study reports the expression in the brain of two CCL27 splice variants localized in the cerebral cortex and limbic regions. CCL27-like immunoreactivity was identified mainly in neurons.

Airborne inflammatory factors: "from the nose to the brain".

The intranasal pathway is a direct route of communication between the environment and the brain. This pathway is currently used for the delivery of several experimental therapeutic peptides and vaccines because it bypasses the blood brain barrier. It is also a route of entrance to the brain for several viruses and toxic substances.